Depression: MFBA

First Generation Anti-psychotics (Typicals)

- Chlopromazine (Thorazine) - Fluphenazine (Prolixin) - Haloperidol (Hadol) - Loxapine (Loxitane) - Perphenazine (trilafon) - Pimozide (Orap) - Thioridazine (Mellaril) - Thiothixene (navane) - Trifluoperazine (Stelazine)

bipolar disorder

A mood disorder in which the person alternates between the hopelessness and lethargy of depression and the overexcited state of mania.

Second Generation Antipsychotics (Atypical)

Aripiprazole (Abilify) Asenapine (Saphris) Clozapine (Clozaril) Iloperidone (Fanapt) Lurasidone (Latudal) Olanzapine (Zyprexa) Paliperidone (Invega) Pimavanser (Nuplazid) Quetiapine (seroquel) Risperidone (risperdal) Ziprasidone (Geoodon)

Which one of the following comorbid conditions is most likely to be seen in patients with depression? An anxiety disorder An eating disorder A personality disorder An alcohol use disorder A nicotine use disorder

Critique: A coexisting DSM-IV disorder is seen in up to 66%-84% of patients with major depression. As a group, anxiety disorders are the most commonly co-occurring psychiatric disorders in patients with major depression. A 2005 epidemiologic survey found that among patients with major depression, 62% also met criteria for generalized anxiety disorder, 52% for social phobia, 50% for posttraumatic stress disorder, and 48% for panic disorder (level of evidence 2). Personality disorders are also common in patients with major depressive disorder, with obsessive-compulsive, paranoid, schizoid, and avoidant personality disorders being most frequent. Major depression is also common in individuals with substance abuse and eating disorders. In the National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC), 14.1% of patients with major depression had an alcohol use disorder and 26% had a nicotine use disorder.

Temperament characteristics associated with a bipolar II outcome in patients initially presenting with an episode of major depression include which of the following? (Mark all that are true.) Lability of mood Excessive use of denial as an ego defense A tendency to engage in intense fantasy or daydreaming Social anxiety A high energy level

Critique: A large, well designed prospective study of patients with major depression found that 12% of those with a unipolar diagnosis developed bipolar illness (usually bipolar II) over 11 years of follow-up. Those ultimately diagnosed with a bipolar illness differed from those remaining unipolar in several important aspects, including temperament. The early-onset (earlier than age 18), habitual, non-impairing traits that identified risk for bipolar outcome included mood lability, energetic activity, a tendency to engage in intense fantasy and daydreaming, and social anxiety. Of these four traits, mood lability was the most specific (86%).

True statements regarding the treatment of major depression in adults include which of the following? (Mark all that are true.) Psychotherapy and antidepressant medication are equally effective in patients with mild depression Psychotherapy is more effective than antidepressant medication for severe depression Combining psychotherapy and antidepressant medication in patients with mild to moderate depression is significantly more cost-effective than either treatment alone Interpersonal therapy (IPT) is the most effective form of psychotherapy Combining psychotherapy with antidepressant medication is likely to be more beneficial than either treatment alone in patients with severe depression

Critique: A nonsystematic review by Thase found that combining antidepressants and psychotherapy was beneficial in moderate to severe depression, but not in mild to moderate depression. Casacalenda performed a systematic review of six randomized, controlled, double-blind trials comparing medication and psychotherapy with placebo. In the medication studies, five used tricyclic antidepressants and one used a monoamine oxidase inhibitor. The psychotherapy studies included three using cognitive-behavioral therapy, three using interpersonal therapy, and one using problem-solving therapy. Intent-to-treat analyses indicated that pharmacotherapy and psychotherapy were significantly more efficacious than control conditions (p <0.0001) but were not significantly different from each other for treating mild to moderate depression. Two subsequent randomized, controlled trials (Keller, DeJonge) showed that combination antidepressant-psychotherapy treatment is more effective than either treatment alone for patients with mild to moderate major depression. However, the Keller study examined patients with chronic depression, refractory depression, or depression recurring during treatment (who by definition have failed first-line treatments). Therefore, the balance of evidence suggests that combination antidepressant-psychotherapy is beneficial in severe major depression, but overall may not be superior to either treatment alone in milder forms of major depression. Since many patients with mild to moderate depression will respond to either antidepressants or psychotherapy alone, and extra resources are required to provide combined treatment to all depressed patients, combining antidepressants and psychotherapy for patients with milder forms of depression should be reserved for those who do not initially respond to either treatment alone. There are few studies directly comparing different types of psychotherapy for major depressive disorder. One systematic review suggested that cognitive therapy may be more effective than interpersonal therapy for major depression, but after poor-quality studies were eliminated the differences disappeared.

An increased risk of depression is associated with which of the following conditions? (Mark all that are true.) HIV infection Stroke Chronic pain syndromes Diabetes mellitus Parkinson's disease

Critique: A number of medical conditions have been linked to the development of depression, including hypothyroidism and myocardial infarction. Depression is observed in one-third to one-half of patients following a stroke, and occurs to some degree in 40%-50% of patients with Parkinson's disease. In primary care settings, a twofold higher risk for depression is seen in patients with pain symptoms. In addition, rates of major depressive disorder are increased in patients with HIV infection compared to HIV-negative individuals. It is unclear whether diabetes mellitus is associated with a higher risk of depression, with meta-analyses and epidemiologic studies yielding mixed results.

A 53-year-old female sees you because of rib pain after a fall, and radiographs reveal an acute nondisplaced fracture of the lateral right 10th rib. She has a history of recurrent major depression that is well controlled with citalopram (Celexa). Which one of the following pain medications would increase her risk of developing serotonin syndrome? Acetaminophen Codeine Ibuprofen Tramadol (Ultram)

Critique: A number of over-the-counter and prescription drugs are associated with serotonin syndrome. Drugs linked to serotonin syndrome as a result of reducing serotonin reuptake include: * SSRIs and SNRIstricyclic antidepressants such as clomipramine and imipramine * St. John's wortanalgesics such as meperidine, fentanyl, tramadol, and pentazacine * antiemetics such as ondansetron and metoclopramide * cough suppressants such as dextromethorphan * antiepileptics such as valproate and carbamazepine Other drugs associated with serotonin syndrome include: * agents that inhibit serotonin breakdown, such as MAO inhibitors * antibiotics such as linezolid and tedizolid, and methylene blue * agents that increase serotonin release, such as CNS stimulants, anorectics, and drugs of abuse such as cocaine * agents that increase serotonin precursors or agonists, such as tryptophan, lithium, fentanyl, and LSD * drugs that inhibit CYP2D6 and CYP3A4 Although it is possible that taking just one drug that increases serotonin levels can cause serotonin syndrome in susceptible individuals, serotonin syndrome occurs most often when two such agents are combined.

Antidepressant therapy has been associated with an increased risk of suicidal thoughts and behaviors in which of the following age groups? (Mark all that are true.) Children Adolescents Young adults Middle-aged adults The elderly

Critique: A potential increase in suicidal thinking and behavior has been demonstrated with the use of antidepressants in children, adolescents, and young adults. For adults over age 65, a reduced risk of suicidal thinking and behavior has been seen, and there is no change in risk in adults 25-64 years of age. Irrespective of age, however, evidence of increased mortality as a result of suicide has not been demonstrated with antidepressant use in any age group. To alert clinicians to the need for vigilance and communication during the initial phase of antidepressant therapy, the FDA issued black-box warnings pertaining to children, adolescents, and young adults that advise of this increased risk for suicidal thinking and behavior (SOR B). When managing the patient with major depressive disorder, this risk needs to be balanced against the negative effects of untreated depression, including suicide, as well as the demonstrated benefits of antidepressant treatment.

Atypical antipsychotics include drugs such as clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). True statements regarding the association between the atypical antipsychotics and treatment-emergent hyperglycemia or diabetes mellitus include which of the following? (Mark all that are true.) Preexisting risk factors for type 2 diabetes mellitus are thought to be a risk factor for this phenomenon Weight gain is always an associated phenomenon Patients on atypical antipsychotics should be monitored at 6, 12, and 18 months for evidence of worsening glycemic control Based on available data, olanzapine and clozapine are associated with the highest risk for treatment-associated hyperglycemia Preexisting diabetes mellitus is a contraindication to the use of atypical antipsychotics

Critique: An association between atypical antipsychotics and treatment-associated hyperglycemia and diabetes mellitus prompted the FDA to issue a class warning in 2003. This warning included the following statement: Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia. Persons with diabetes who are started on atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing. The association between these drugs and diabetes is based on case reports and retrospective cohort studies, largely in schizophrenic patients. These studies were of heterogeneous design, limiting the conclusions that could be drawn. It should be noted that both schizophrenia and bipolar illness impart a two- to threefold increase in rates of diabetes mellitus compared with the general population apart from treatment interventions, and weight gain is not always associated with the phenomenon. The mechanism and relative contribution that atypical antipsychotics might make to the development of hyperglycemia and diabetes mellitus, risk factors that accurately identify such patients, and any differential effect among various members of the medication class have yet to be determined in prospective controlled studies. The American Diabetes Association, American Psychiatric Association, and other groups convened a consensus panel that made recommendations regarding the clinical assessment of patients treated with such agents. Based on available data, clozapine and olanzapine were found to have the most consistent association with treatment-emergent hyperglycemia and diabetes mellitus. The panel recommended baseline assessment for the presence of metabolic syndrome and known risk factors for diabetes (family history, BMI, waist circumference, blood pressure, fasting plasma glucose) and periodic reassessment during therapy. A repeat fasting plasma glucose level is recommended at 12 weeks and annually thereafter. These guidelines serve as a minimum recommendation. Others suggest more frequent measurements of plasma glucose. Patients already diagnosed with diabetes mellitus may be treated with atypical antipsychotics. For these patients, use of an agent appearing to have a lower propensity for weight gain and glucose intolerance may be preferable. Vigilance for evidence of deteriorating glycemic control is mandatory.

A 79-year-old male with a history of hypertension and benign prostatic hyperplasia is diagnosed with major depressive disorder. His current medications are enalapril (Vasotec), 20 mg/day, and finasteride (Proscar), 5 mg/day. Which of the following antidepressants should be avoided in this patient? (Mark all that are true.) Amitriptyline Duloxetine (Cymbalta) Sertraline (Zoloft) Trazodone (Oleptra) Bupropion (Wellbutrin)

Critique: Benign prostatic hyperplasia (BPH) and other potential causes of bladder outlet obstruction are relative contraindications to the use of antidepressant medications with antimuscarinic properties. For this reason, trazodone, tertiary amine tricyclic antidepressants such as amitriptyline, and MAO inhibitors are best avoided in patients with significant BPH (SOR C). Serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine), SSRIs, and bupropion do not possess antimuscarinic activity and would be less likely to cause urinary retention.

Agents approved by the FDA for the treatment of mania in patients with bipolar disorder include which of the following? (Mark all that are true.) Lithium Divalproex (Depakote) Olanzapine (Zyprexa) Lamotrigine (Lamictal) Risperidone (Risperdal)

Critique: Bipolar disorder is a severe psychiatric disorder that is characterized by recurrent manic, mixed, and depressive episodes. There are several FDA-approved agents for the treatment of mania in patients with bipolar disorder. Lithium was approved in 1970, chlorpromazine in 1973, and divalproex in 1994. Since the approval of olanzapine in 2000, other atypical antipsychotics, including risperidone (2003), quetiapine (2004), ziprasidone (2004), and aripiprazole (2004), have been added to the list of agents approved by the FDA for the treatment of acute mania. Although it is FDA approved for maintenance treatment of bipolar disorder, lamotrigine is not FDA approved for the treatment of acute mania.

You prescribe antidepressants for a 37-year-old female for major depression of moderate severity. When you see her 8 weeks later for a follow-up visit she is sleeping better, concentrating better at work, and not overeating as much as she was. However, she is still fatigued and has poor self-esteem, has not resumed her social activities, and feels "a little" depressed. You administer a standardized depression questionnaire, and conclude the patient has achieved partial remission. Laboratory findings are normal. At this point, appropriate treatment options include which of the following? (Mark all that are true.) Maintain the current medication dosage and see her back in 4 weeks Increase the dosage of her medication Change medications Stop treatment and refer to specialty behavioral health care Recommend adjunct psychotherapy Augment with another medication

Critique: Conventional wisdom has led clinicians to institute a change in treatment when patients have failed to achieve symptom remission after 8 weeks of adherence to antidepressant treatment. While treatment changes are still an option, the STAR*D trial found that a substantial number of patients did not achieve symptom response or remission until after 8 weeks of therapy. Therefore, continuing current treatment, with subsequent follow-up, is a reasonable treatment option. The Kaiser Permanente 2006 Guidelines for Treatment of Major Depression in Primary Care list the following treatment options for patients with major depressive disorder whose symptoms fail to remit after first-line treatment: * combining antidepressants and psychotherapy * increasing the dosage of the initial antidepressant * combined treatment with SSRIs and low-dose desipramine * switching to a different antidepressant of the same or a different class * augmenting with low-dose lithium (300-600 mg/day) Of these, combining antidepressants and psychotherapy has the best evidence for efficacy, based on data from a population of chronically depressed patients (whose symptoms by definition had failed to resolve after initial depression treatment). The Kaiser Permanente guideline found weak evidence for the effectiveness of increasing the dosage of the initial antidepressant, switching antidepressants, and augmenting with low-dose lithium. BMJ Clinical Evidence found insufficient evidence to recommend the addition of lithium. However, lithium was found to be an effective augmentation strategy in the STAR*D trial. Although antidepressant combinations are sometimes used in clinical practice, Kaiser Permanente found evidence of effectiveness only for combining SSRIs with desipramine. Combining antidepressants should be done carefully, and patients should be monitored for possible serotonergic side effects or tricyclic antidepressant toxicity (especially cardiac arrhythmias). There is not sufficient evidence for using pindolol or buspirone for antidepressant augmentation. Until recently, the evidence regarding buspirone for antidepressant augmentation had been based mostly on case studies or observational trials, but the randomized, controlled STAR*D trial found that buspirone augmentation could be beneficial.

Which one of the following is true regarding the relationship between stressful life events and the onset of major depressive disorder? The genetically influenced traits that predispose patients to major depressive disorder have a protective effect on the response to stressful events Stressful life events are associated with the onset of major depressive disorder Stressful life events play a minimal role in the onset of major depressive disorder

Critique: Independent stressful life events have a substantial causal relationship with the onset of major depressive disorder. In spite of this relationship, about one-third of the association between stressful life events and depression is noncausal, since some patients who are predisposed to develop major depression select themselves into high-risk environments. These individuals do not experience stressful life events at random, but possess a genetically influenced set of traits that increase their tendency to place themselves into high-risk environments likely to produce stressful events, in addition to increasing their vulnerability to major depressive disorder.

A 68-year-old male with diabetes mellitus and hypertension has a past history of major depressive disorder but has not been depressed recently. He and his wife ask you about the possibility that his depression may return and become a significant problem. Which of the following would be accurate advice when discussing their concerns? (Mark all that are true.) Depression is a normal part of the aging process and does not require treatment at this man's age Depression that occurred more than 20 years ago does not increase the patient's risk for a recurrence now Suicide risk is higher in elderly patients when depression is untreated, compared to the risk in untreated younger patients with depression Depression secondary to a chronic medical illness, such as myocardial infarction or diabetes mellitus, rarely requires treatment with an antidepressant and will remit as the chronic medical disease improves

Critique: Depression in elderly patients is often inappropriately assumed to be secondary to functional limitations or chronic disease burden, but it deserves accurate diagnosis and effective treatment irrespective of life circumstances or chronic disease comorbidity. The association of a wide range of central nervous system lesions in elderly depressed patients is one indication of the legitimate pathophysiologic basis of this disease. A past history of depression is always an important risk factor, irrespective of age. The risks for both attempted suicide and completed suicide are higher in the elderly than in younger patients, contrary to the misperceptions of many physicians, and should be seriously considered in severely depressed elderly patients.

A 24-year-old female presents with a 10-month history of sadness, anhedonia, daily exhaustion, early morning awakening, increased appetite, and crying with little provocation. Her past medical history reveals a history of polycystic ovary syndrome, and the physical examination is notable for a mildly hirsute female with a BMI of 32.4 kg/m2. You make a diagnosis of major depression. Which one of the following antidepressants would most likely help the patient lose weight? Tranylcypromine (Parnate) Imipramine (Tofranil) Paroxetine (Paxil) Mirtazapine (Remeron) Bupropion (Wellbutrin)

Critique: Depression is commonly seen in obese individuals. Rates of depression appear particularly high in obese women and those with a BMI >40 kg/m2. When selecting an antidepressant for individuals with major depressive disorder who are overweight or obese, the potential impact of treatment on weight should be considered. Mirtazapine, tricyclic antidepressants, and MAO inhibitors are associated with the greatest tendency for weight gain. Weight gain also occurs in some patients taking SSRIs, particularly paroxetine, and can sometimes be substantial. Bupropion, however, is generally weight neutral and has been associated with modest weight reduction when used by obese patients with major depression (SOR C).

True statements regarding the prevalence and nature of depression in the elderly include which of the following? (Mark all that are true.) Depression is more common in the elderly than in younger adults Physicians are more likely to correctly diagnose depression in elderly patients than in younger patients Treatment of depression in the elderly is less important than in younger patients because the depression is generally less severe Patients who are elderly when their first episode of depression occurs have a relatively high likelihood of developing chronic or recurring depression

Critique: Depression is not a part of normal aging and is actually less common in the elderly than in younger patients. Physicians are often less likely to diagnose and treat depression appropriately in the elderly because they assume that all elderly patients are somewhat depressed. Somewhat paradoxically, a patient who develops major depressive disorder for the first time in later life actually has a much higher risk of recurrence or chronicity, probably because of both social support deficiencies and neurochemical abnormalities.

Deficiencies in which of the following neurotransmitters have been linked to the development of depression? (Mark all that are true.) Dopamine Norepinephrine Acetylcholine Serotonin Histamine

Critique: Differing patterns of neurotransmitter abnormalities in various brain regions have been linked to the development of depression. Deficiencies in serotonin, norepinephrine, dopamine, α-aminobutyric acid, brain-derived neurotrophic factor, somatostatin, and thyroid-related hormones have been proposed as contributing to the development of depression. Conversely, overactivity in neurotransmitter systems involving acetylcholine, corticotropin-releasing factor, and substance P may have a role in the causation of depression.

Appropriate advice for patients when first prescribing antidepressants for major depression includes which of the following? (Mark all that are true.) Antidepressants should be stopped as soon as any side effects are noted Antidepressant side effects such as nausea, anxiety, and dry mouth are likely to persist for 6-12 weeks Antidepressants should be continued even after symptoms of depression have resolved If the full effect of medication has not been reached after 4 weeks, a medication change will be necessary

Critique: Early antidepressant discontinuation is associated with early symptom relapse. Both randomized, controlled trials and observational trials show that patients often discontinue antidepressants. National observational data suggest that only 70%-75% of patients continue antidepressants for 3 months, and 50%-60% continue them for 6 months. Patients often discontinue antidepressants because they do not recall being told to continue them after their symptoms improve. Many antidepressant side effects such as nausea, dry mouth, and anxiety are mild and will abate with continued treatment. While some symptoms of depression, such as sleep disturbance, might improve shortly after starting antidepressants, the full effect of antidepressant medication may not be achieved for 6-8 weeks or longer. Patients who received specific instructions about taking antidepressants continued the medication for longer periods of time. These instructions should include advice to continue taking medication after depressive symptoms have resolved, information on the transient nature of many side effects, and directions to seek medical advice before stopping antidepressants.

You are treating a 53-year-old female for her first episode of major depression. After 6 weeks of treatment with antidepressants, all depressive symptoms have resolved. Evidence suggests that the TOTAL length of treatment with antidepressants for this patient should be AT LEAST 3 months 6 months 12 months 18 months

Critique: Early discontinuation of antidepressants is associated with an early relapse of depression symptoms. A systematic review found that in people who had responded to antidepressants after 2 months of treatment, the number needed to treat by continuing antidepressants to prevent one additional relapse was 6 over 6 months (95% CI: 5-8), 5 over 12 months (95% CI: 4-6), and 4 over 24-36 months (95% CI: 3-7). However, this review did not elucidate whether patients with milder forms of major depression derive as much benefit from longer treatment with antidepressants as patients with moderate or severe forms of major depression.

A 56-year-old female is diagnosed with major depression. Her past medical history is notable for chronic hypertension and a history of breast cancer 6 months ago, treated with segmental mastectomy followed by breast irradiation. Her current medications are enalapril (Vasotec), 10 mg daily, and tamoxifen (Soltamox), 20 mg daily. Which of the following antidepressants should be avoided? (Mark all that are true.) Paroxetine (Paxil) Citalopram (Celexa) Mirtazapine (Remeron) Desvenlafaxine (Pristiq) Fluoxetine (Prozac)

Critique: Factors to consider when choosing an antidepressant include past response to an agent, patient preference, co-occurring psychiatric and medical illnesses, relative efficacy and effectiveness, cost, half-life, safety, tolerability, anticipated side effects, and potential for drug interactions. Antidepressants differ in their interactions with the cytochrome P-450 (CYP) system and their metabolism, as well as inhibition of specific CYP enzymes. Tamoxifen is metabolized by the cytochrome P-450 2D6 (CYP2D6) isoenzyme to endoxifen (4-hydroxy-N-desmethyltamoxifen), the active metabolite that may be responsible for much of tamoxifen's antiestrogenic activity. Paroxetine and fluoxetine are strong inhibitors of CYP2D6 and thus would likely cause a reduction in tamoxifen's active metabolite and therefore possibly lead to poorer patient outcomes (SOR C).

A 36-year-old male is diagnosed with major depressive disorder. He currently smokes 2 packs of cigarettes a day and would like to quit. Antidepressants that have been shown to facilitate smoking cessation include which of the following? (Mark all that are true.) Citalopram (Celexa) Bupropion (Wellbutrin) Mirtazapine (Remeron) Nortriptyline (Pamelor) Doxepin

Critique: For individuals with nicotine dependence who wish to stop smoking, bupropion and nortriptyline treatment have been shown to increase smoking cessation rates by about twofold. This is an important consideration when selecting a specific antidepressant for a smoker with major depressive disorder.

A 35-year-old female is brought to the emergency department by her husband with a 6-hour history of tachypnea, confusion, and agitation. Her husband reports that she was involved in a motor vehicle accident last night when her car was rear-ended. She was seen at an urgent-care clinic where she was diagnosed with "whiplash" and given prescriptions for tramadol (Ultram) for pain and cyclobenzaprine (Flexeril) for muscle spasm. The patient also has a history of depression, currently treated with sertraline (Zoloft) and olanzapine (Zyprexa). Which of the following would support a diagnosis of serotonin syndrome in this situation? (Mark all that are true.) Constricted pupils "Lead-pipe" rigidity Xerostomia Clonus Hyperthermia

Critique: For patients taking psychotropic medications, the possibility of serotonin syndrome, anticholinergic syndrome, or neuroleptic malignant syndrome (NMS) warrants consideration in those developing altered mental status associated with neuromuscular and autonomic nervous system dysfunction. All three conditions are associated with hyperthermia, hypertension, tachycardia, and tachypnea. The pupils are dilated in serotonin syndrome and anticholinergic syndrome but normal in NMS. Although flushed, the skin and the mucous membranes are dry in anticholinergic syndrome, whereas diaphoresis and sialorrhea are typically seen in serotonin syndrome and NMS. Serotonin syndrome is distinguished by increased neuromuscular tone in the extremities, with hyperreflexia and clonus. "Lead-pipe" rigidity and reduced reflexes are typically seen in NMS, whereas muscle tone and reflexes are normal in anticholinergic syndrome.

A 64-year-old female presents with a complaint of episodic irregular heartbeats and dizziness. Her past medical history is notable for a 4-month history of major depression currently treated with citalopram (Celexa), 60 mg daily. Which one of the following cardiac dysrhythmias is the most likely cause of her symptoms? Sick sinus syndrome Intermittent Mobitz type II heart block Paroxysmal atrial tachycardia Torsades de pointes Nonsustained ventricular tachycardia

Critique: In August 2011, the FDA issued a drug safety communication warning health care professionals that the antidepressant citalopram should no longer be used at dosages above 40 mg daily. Citalopram has been found to be associated with dose-dependent QT interval prolongation, and the FDA concluded based on post-marketing reports that dosages greater than 40 mg daily can lead to abnormal heart rhythms, including torsades de pointes. Moreover, studies have failed to demonstrate a benefit in the treatment of depression with these higher dosages. Citalopram should not be used in patients with congenital long QT syndrome or in patients with conditions placing them at higher risk for developing torsades de pointes (e.g., heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia). In addition, the FDA has advised that a maximum dosage of 20 mg daily be used in patients with hepatic impairment, those older than 60, poor metabolizers of cytochrome P-450 isoenzyme 2C19, and patients taking concomitant cimetidine (SOR C). Any of these factors can lead to higher blood levels of citalopram.

Which one of the following is the strongest risk factor for the development of major depression in the elderly? A personal history of major depression The onset of a new chronic disease The death of a spouse A marked decrease in the independent activities of daily living (IADL) score

Critique: In community-residing elderly patients, increased age, personal history of depression, the death of a spouse, health-related factors, and co-morbid organic brain disorders or anxiety syndromes are significantly related to depression incidence. Death of a spouse is the strongest risk factor. Having a spouse, and if unmarried having social support, significantly reduces the impact of functional disabilities on the incidence of depression.

True statements regarding comorbid depression and coronary artery disease (CAD) include which of the following? (Mark all that are true.) Patients with CAD have a prevalence of major depressive disorder in the range of 40%-50% Patients with CAD and comorbid depression have a twofold to threefold increased risk of future cardiac events when compared to nondepressed controls Independent of other risk factors in patients initially free of CAD, the relative risk for the development of CAD conferred by depression is 3.5-4.0 The prevalence of major depressive disorder is inversely related to elevations in LDL-cholesterol Comorbid depression is associated with greater platelet activation

Critique: In patients with coronary artery disease (CAD), the prevalence of major depressive disorder is 17%-27%. A larger percentage has subsyndromal symptoms of depression. Patients with depression have a twofold to threefold increased risk for future coronary events, independent of baseline cardiac function. In patients initially free of CAD, the relative risk for CAD conferred by depression, independent of other risk factors, is 1.5. Potential biological mechanisms by which depression can lead to cardiac events include alterations in cardiac autonomic tone, greater platelet activation, increased catecholamine levels, inflammatory processes, and lower omega-3 fatty acid levels. Potential behavioral mechanisms include dietary factors, lack of exercise, medication nonadherence, unhealthy lifestyle, and poor social support.

True statements regarding major depressive disorder include which of the following? (Mark all that are true.) Patients with major depressive disorder have high levels of psychiatric comorbidity The mean duration of an episode of untreated major depression is 8 weeks Over 50% of non-institutionalized patients with major depressive disorder receive appropriate evidence-based treatment The risk of developing major depressive disorder is highest in the preteen years

Critique: Major depressive disorder has been found to be associated with high levels of psychiatric comorbidity and high levels of role impairment. The risk of developing this disorder is low until the early teens. The National Comorbidity Survey Replication found that only 22% of patients received appropriate treatment, and that the mean episode duration was 16 weeks.

Which of the following elements would support a diagnosis of major depressive disorder with atypical features? (Mark all that are true.) Insomnia Excessive sleepiness Mood improvement in response to positive events Weight gain Akathisia

Critique: Major depressive disorder with atypical features is a subtype of major depression. Criteria for the diagnosis include the presence of marked mood reactivity (i.e., improvement in mood in response to actual or potential positive events) and two or more of the following: significant weight gain or increase in appetite, hypersomnia, leaden paralysis (a heavy, leaden feeling in the arms or legs), and a long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment (SOR C). In major depressive disorder with atypical features, MAO inhibitors have greater efficacy than tricyclic antidepressants. Other options include SSRIs, bupropion, cognitive-behavioral therapy, and electroconvulsive therapy.

An 82-year-old female with a 3-month history of sadness, anorexia, weight loss, and insomnia is diagnosed with major depression. The physical examination is notable for an anxious, frail appearance, with a BMI of 19.2 kg/m2 and a blood pressure of 170/80 mm Hg. An EKG shows a normal sinus rhythm, bifascicular block, a PR interval of 0.24 sec, and right bundle branch block. Which one of the following antidepressants would be preferred? Bupropion (Wellbutrin) Fluoxetine (Prozac) Venlafaxine Mirtazapine (Remeron) Imipramine (Tofranil)

Critique: Mirtazapine has sedative properties and is associated with weight gain. It would not only treat the patient's depression, but would address her insomnia and weight loss as well. While they have comparable antidepressant efficacy, SSRIs such as fluoxetine, SNRIs such as venlafaxine, and bupropion are more activating than mirtazapine and can cause insomnia. In addition, a dose-related rise in blood pressure is seen with SNRIs, particularly venlafaxine. Cardiovascular side effects, including arrhythmias, are a potential problem with tricyclic antidepressants such as imipramine, and their use is therefore contraindicated in many patients with heart disease. In particular, tricyclic antidepressants act as class Ia antiarrhythmic agents and are thus best avoided in patients with preexisting cardiac conduction abnormalities.

True statements regarding epidemiologic factors related to bipolar disorder and major depressive disorder include which of the following? (Mark all that are true.) The lifetime prevalence rate for major depressive disorder is approximately twice that of bipolar disorder The mean age of onset for major depressive disorder is between the ages of 25 and 35 The age of onset of bipolar disorder is 6 years earlier on average than the onset of major depressive disorder Bipolar disorder is approximately twice as common in females as in males

Critique: Mood disorders in the bipolar spectrum affect a significant number of primary care patients. Recent investigations of depressed and anxious primary care patients suggest that 25%-30% have some form of bipolar disorder, often a soft (non-manic) disorder such as bipolar II disorder. In one investigation, 9.8% of randomly selected waiting-room patients screened positive for bipolar illness. These patients usually present with a depressed mood and are incorrectly diagnosed with major depression or an anxiety or substance use disorder. Querying patients and their significant others for histories of manic symptoms, in addition to evaluation of family history, the longitudinal course of the illness, and treatment response to previous antidepressant therapy, will usually confirm the diagnosis. A review of the epidemiology of depression and bipolar disorder in several countries found that the prevalence of major depressive disorder ranged from 1.5% to 19.0%. The prevalence of bipolar disorder ranged from 0.3% to 1.5%. The mean age of onset was 24.8-34.8 years for major depression. The age of onset for bipolar disorder was found to be 6 years earlier on average than that of major depression. Whereas rates of major depressive disorder were found to be higher for women than men, rates of bipolar disorder were nearly equal. Misdiagnosis often leads to somatic treatment with single or combination antidepressant therapy. In patients with bipolar illness this can lead to treatment-emergent manic/hypomanic episodes, the development of rapid cycling (and, therefore, treatment refractory states), or mixed states characterized by concurrent manic and depressed symptomatology. Delays in making the correct diagnosis, or the provision of unfocused treatment, may leave patients at high risk for the increased morbidity and mortality that characterizes untreated bipolar illness.

Which one of the following instruments allows simultaneous assessment of both DSM-IV depression criteria and symptom severity, and is useful for follow-up? The nine-item Patient Health Questionnaire (PHQ-9) The Beck Depression Inventory (BDI) The Center for Epidemiologic Studies Depression Screen (CES-D) The Zung Depression Scale (ZDS) The Primary Care Evaluation of Mental Disorders (PRIME-MD)

Critique: Numerous instruments have been developed to assist the primary care clinician in identifying patients with depression. The ZDS, BDI, CES-D, and PHQ-9 all have the advantage of being designed for patients to complete on their own in 5 minutes or less, and each yields a score that rates the severity of patient symptoms. Standard cutoff scores for these instruments correspond to a high likelihood of depression. The PRIME-MD assesses multiple mental health disorders and begins with a questionnaire completed by the patient, followed by modules that are administered by a clinician. The PRIME-MD depression module directly assesses DSM-IV depression criteria, but does not yield a severity score. The PHQ-9 is unique in that its individual questions are based on the current DSM-IV Major Depressive Disorder criteria, and it can therefore be used to assess whether these criteria are met, while also giving an overall severity score. The PHQ-9 also exhibits superior performance characteristics in primary care. Its positive predictive value (PPV) of 55% is superior to that of other screening instruments, which have PPV ranges from 21%-50% in primary care settings. This ensures the lowest number of false-positive screens. However, clinician confirmation of positive screens is required for all of these instruments. (level of evidence 1: Good quality patient-oriented evidence)

The lifetime prevalence of major depressive disorder in the U.S. population is 2%-5% 5%-10% 10%-20% 20%-30%

Critique: The National Comorbidity Survey Replication found a lifetime prevalence of major depressive disorder in the U.S. population of 16.9%. The 12-month prevalence was 10%.

True statements regarding suicide attempts among patients with a major depressive episode include which of the following? (Mark all that are true.) Women successfully commit suicide at a higher rate than men Patients hospitalized for suicidality have a markedly increased lifetime risk of suicide compared to patients managed in an outpatient setting Patients with depressive disorders have suicide prevalence rates similar to those of the general population Depressed cigarette smokers attempt suicide more frequently than depressed nonsmokers Increased subjective assessment of depression by the patient is associated with an increased risk for a suicide attempt

Critique: Patients with mood disorders have a higher risk of suicide than the general population. There is a hierarchy of risk among patients with depressive disorders, based on the intensity of treatment. In one study, patients who had been hospitalized specifically for suicidality had a lifetime prevalence of suicide of 8.6%. Patients with histories of hospitalization without suicidality had a lifetime prevalence of suicide of 4.0%. Patients who received outpatient care for their mood disorder had a suicide prevalence of 2.2%. The prevalence of suicide in the general population was less than 0.5%. Risk factors related to suicidal acts in patients with major depressive episodes include the following: * a previous history of a suicide attempt * the patient's subjective assessment of the severity of * depression * hopelessness * the number of perceived reasons for living * the presence of comorbid substance use disorders, * including cigarette smoking * the presence of a cluster personality disorder * impulsivity * aggression These factors are important in the risk assessment for suicide in patients with major depressive episodes.

A 26-year-old gravida 1 para 1 sees you for routine follow-up 6 weeks after a vaginal delivery. She begins to weep during the visit and reveals that over the past few weeks she has grown increasingly unhappy and overwhelmed. She says her baby seems to consume all of her time and causes her to feel "trapped" and "tied down." She finds it harder to concentrate on tasks such as making the baby's formula, and her husband complains that she no longer gets things done. Despite being exhausted, she has difficulty falling asleep. At times she becomes angry with herself for being "so inept." She admits that she sometimes feels afraid to be alone with the baby because of fleeting thoughts of harming him. True statements regarding this situation include which of the following? (Mark all that are true.) Postpartum depression can result in delays in infant development Maternal fears of harming the baby are uncommon A score of 7 on the Edinburgh Depression Scale supports the diagnosis of postpartum depression Antidepressant therapy can be prescribed even if the mother is breastfeeding Psychotherapy is considered to be ineffective

Critique: Postpartum depression, which includes major and minor depression, has an incidence of 6.5%-12.9% in the first year following the birth of a child. Important risk factors include a history of major depression during a prior pregnancy, antenatal depressive symptoms, a past history of major depression, poor social support, and major events or life stressors during the pregnancy. Possible consequences of postpartum depression include child abuse and neglect; early cessation of breastfeeding; family dysfunction; adverse effects on cognitive, social-emotional, and behavioral development in the child; and increased costs of medical care. Both the American Academy of Pediatrics and the American Congress of Obstetricians and Gynecologists support screening for depression in the postpartum period. The Edinburgh Postpartum Depression Scale, a simple 10-question instrument completed by the mother, is the most commonly used validated screening tool for postpartum depression. A score of 10-12 or greater on this scale supports the diagnosis of postpartum depression. Unlike the baby blues, which begin during the first few days following delivery and resolve within 10 days, postpartum depression starts later and lasts longer. Although its diagnostic criteria are the same as those for depression unrelated to pregnancy, women with postpartum depression are less likely to report feeling sad. Up to 60% of women with postpartum major depression have obsessive thoughts focusing on aggression toward the infant. As in all patients with major depression, suicide risk should be assessed and monitored. Pharmacotherapy with antidepressant medication is regarded as the mainstay of treatment for moderate to severe postpartum depression. Although long-term data is lacking, antidepressant therapy is considered compatible with breastfeeding (SOR C). Psychotherapy is effective as an alternative to pharmacotherapy for mild to moderate postpartum depression and as adjunct therapy with medication in moderate to severe depression.

A 32-year-old female informs you that she and her husband have decided to have a child. She was diagnosed with major depression 3 months ago, but it has been well controlled with paroxetine (Paxil). She had a previous episode of major depression 10 years ago that also responded to paroxetine. She asks what effect antidepressant use would have on her pregnancy. Accurate advice would include which of the following? (Mark all that are true.) Pregnancy has been shown to have a salutary effect on major depressive disorder Paroxetine use during pregnancy has been linked to an increased risk of congenital heart malformations Paroxetine use in pregnancy has been linked to an increased risk for cleft palate SSRI use during the first trimester of pregnancy is associated with a higher risk of persistent pulmonary hypertension in the newborn Euthymic women who discontinue antidepressant therapy during pregnancy have a fivefold higher risk of relapse over the course of pregnancy compared with women who continue their antidepressant

Critique: Pregnancy has not been shown to have a salutary effect on major depression. A prospective naturalistic investigation of the risk of relapse of depression in pregnant women on antidepressant therapy showed a fivefold higher risk of relapse in pregnant women who discontinued antidepressant therapy compared to those who continued their medication over the course of the pregnancy. Primarily because of unpublished reports from the Swedish Medical Birth Registry and a large HMO database showing a 50%-100% increased risk for cardiovascular malformations (ventricular and atrial septal defects) after antenatal exposure to paroxetine, in the fall of 2005 the FDA changed paroxetine from pregnancy category C to category D. Although the National Birth Defects Prevention Study failed to demonstrate that maternal SSRI use during pregnancy resulted in a higher risk of congenital heart defects, a small absolute increased risk for craniosynostosis, omphalocele, and anencephaly was seen. These latter findings, however, were not corroborated by the Slone Epidemiology Center Birth Study. Both of these studies reported a possible association of paroxetine with congenital right ventricular outflow tract obstruction defects. Persistent pulmonary hypertension in the newborn has been linked to maternal use of SSRIs, but during late pregnancy.

A 55-year-old male is showing signs of major depressive disorder after a myocardial infarction. True statements regarding this situation include which of the following? (Mark all that are true.) Depression has been shown to be an etiologic factor in the development of ischemic heart disease The depression will most likely resolve as the patient recovers from the myocardial infarction Major depression is a significant predictor of short-term mortality from ischemic heart disease Major depression is a significant predictor of long-term mortality from ischemic heart disease Psychosocial interventions have been shown to be effective in improving depression in myocardial infarction survivors

Critique: Several epidemiologic studies, both prospective and retrospective, have shown significant co-occurrence between depression and ischemic heart disease, as well as predictive relationships between major depressive disorder and both short-term and long-term mortality from ischemic heart disease. Some studies even suggest that the presence of major depressive disorder at the time of hospital discharge after myocardial infarction or unstable coronary syndrome is one of the most powerful predictors of short-term mortality. Depression does not appear to be merely an emotional reaction to the stress of new-onset heart disease, but a significant comorbidity that influences the outcome of heart disease. Although there is strong evidence that both psychosocial interventions and SSRIs improve depression in MI survivors, it has not been proven that appropriate treatment of depression decreases mortality or cardiac events.

Which one of the following is true regarding the effectiveness of antidepressants for treating major depression? SSRIs are the most effective class of antidepressants Tricyclic antidepressants (TCAs) are the most effective class of antidepressants Serotonin-noradrenalin reuptake inhibitors (SNRIs) such as venlafaxine are the most effective class of antidepressants Dopamine antagonists (DAs) such as bupropion (Wellbutrin) are the most effective class of antidepressants SSRIs, SNRIs, and DAs are more effective than TCAs All classes of antidepressants are equally effective

Critique: Several systematic reviews have compared the effectiveness of different classes of antidepressants for treatment of major depressive disorder. Overall, antidepressants are more effective than placebo for treatment of major depressive disorder; tricyclic antidepressants, SSRIs, and newer antidepressants (dopamine antagonists, serotonin-noradrenalin reuptake inhibitors) are, on a population level, equally effective in reducing depressive symptoms and achieving remission of major depression.

A 55-year-old female is diagnosed with mild depression. She states that she would rather not take prescription drugs and prefers a complementary/alternative treatment.Complementary treatments found to be helpful in treating depression include which of the following? (Mark all that are true.) Exercise Tai chi Meditation Yoga Qigong

Critique: Several systematic reviews, including a Cochrane meta-analysis, have reported a significant reduction of depression symptoms with exercise, particularly high-energy aerobic or resistance training. A smaller number of trials suggest that yoga may be an effective intervention as well. Tai chi, qigong, and meditation have not been found to be effective as alternative treatments for the management of depression (SOR B).

A 20-year-old female is diagnosed with depression. The only medication she currently takes is a generic low-dose oral contraceptive containing 20 µg of ethinyl estradiol and 0.1 mg of levonorgestrel. The patient plans to begin psychotherapy and says she would prefer trying an over-the-counter herbal medication before being prescribed an antidepressant. Which one of the following complementary medications can reduce the efficacy of her oral contraceptive? SAM-e (S-adenosyl methionine) Folate St. John's wort An omega-3 fatty acid

Critique: St. John's wort is an herb of the plant species Hypericum perforatum that is widely used as an alternative/complementary treatment for depression. However, the data on the efficacy of St. John's wort for treating depression is somewhat confusing, mixed, and subject to criticism due to concerns regarding the lack of standardized preparations, adequacy of blinding of patients, short study durations, and inclusion of patients not meeting the criteria for major depression. Most studies do show benefit compared with placebo for mild depressive syndromes (including many patients without major depressive disorder who may not require treatment with medication). However, the evidence is mixed when analyses of St. John's wort compared to placebo are restricted to patients with major depressive disorder. Some studies do suggest that St. John's wort is as effective as SSRIs and low-dose tricyclic antidepressants for patients with mild to moderate major depression. Side effects associated with St. John's wort appear to be fewer than with standard antidepressants, but there is a potential for important drug-drug interactions. Combining St. John's wort with an SSRI poses an increased theoretical risk for serotonin syndrome. In addition, St. John's wort has been shown to induce the activity of cytochrome P-450 3A4 enzymes. Induction of this subset can result in reduced efficacy of medications metabolized by them, including oral contraceptives, statins, antiretroviral agents, immunosuppressants, anticoagulants, and hormone replacement therapy (SOR C).

True statements regarding the relationship between depression and the hypothalamic-pituitary-adrenal axis include which of the following? (Mark all that are true.) Hypothalamic-pituitary-adrenal dysfunction is seen in the majority of patients with depression Elevated plasma cortisol levels can be seen in depression Suppressed corticotropin-releasing hormone levels in the cerebrospinal fluid have been linked to depression Hippocampal enlargement is associated with depression

Critique: Stressful life events have been identified as an important risk factor in the development of major depressive disorder. The response to stress has been called the general adaptation syndrome, and evidence points to the neuroendocrine response being mediated through the hypothalamic-pituitary-adrenal axis. Stress results in the release of corticotropin-releasing hormone (CRH) onto pituitary receptors. Depression, being a form of stress, has thus been associated with elevated cortisol levels in plasma and elevated CRH in the cerebrospinal fluid. In addition, the normal cortisol-suppression response to the administration of dexamethasone appears to be absent in half of the most severely depressed patients. Elevated levels of glucocorticoids can reduce the neurogenesis normally seen in the hippocampus and have been suggested as a mechanism for the hippocampal atrophy seen on MRI images of the brain in many patients with depression. It should be noted, however, that depression is a heterogeneous disorder and that most patients treated for depression have no evidence of hypothalamic-pituitary-adrenal dysfunction.

A 27-year-old female presents to your office as a new patient. She has a history of major depressive disorder and irritable bowel syndrome. At present she is not under treatment and her depression is moderately severe. She has a family history of obsessive-compulsive disorder, major depressive disorder, migraine headaches, and fibromyalgia. Which of the following would apply to this patient? (Mark all that are true.) The clustering of diagnoses in the patient's family probably has an underlying biologic basis mediated by serotonin Abnormalities in the cholinergic neurotransmitter system have been implicated in the primary pathophysiology of both of the patient's diagnoses The primary cause of this patient's major depressive disorder is learned or modeled behavior In this patient, a course of interpersonal psychotherapy is indicated prior to starting a trial of antidepressant medication

Critique: Studies have shown that major depressive disorder and other medical and psychiatric disorders aggregate strongly in families. These clustered disorders are referred to as affective spectrum disorder. Affective spectrum disorder comprises major depressive disorder, attention deficit/hyperactivity disorder, bulimia nervosa, dysthymic disorder, fibromyalgia, generalized anxiety disorder, irritable bowel syndrome, migraine, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social phobia. These disorders likely share a common set of causal factors, and all respond to multiple classes of antidepressant medications that have a primary effect on the monoamine neurotransmitter system.

Which of the following disorders will respond to a medication that has its primary action on the serotonin and/or norepinephrine neurotransmitter systems? (Mark all that are true.) Dysthymic disorder Fibromyalgia Schizophrenia Irritable bowel syndrome Attention deficit/hyperactivity disorder

Critique: Studies have shown that major depressive disorder and other medical and psychiatric disorders aggregate strongly in families. These clustered disorders are referred to as affective spectrum disorder. Affective spectrum disorder comprises major depressive disorder, attention deficit/hyperactivity disorder, bulimia nervosa, dysthymic disorder, fibromyalgia, generalized anxiety disorder, irritable bowel syndrome, migraine, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social phobia. These disorders likely share a common set of causal factors, and all respond to multiple classes of antidepressant medications that have a primary effect on the monoamine neurotransmitter system.

A 45-year-old female presents during the month of May with a severe major depression. She is tearful and expresses thoughts of hopelessness. She admits to thinking about suicide from time to time, but agrees to a "no-harm" contract. There are adequate psychosocial supports in place to allow outpatient treatment to proceed.True statements regarding this situation include which of the following? (Mark all that are true.) Her risk of suicide will likely decrease during the first week of antidepressant treatment Her suicide risk is lowered by her presentation in the spring The "no-harm" contract allows the next follow-up visit to be scheduled in 3-4 weeks A family history of suicide would increase her risk for a suicide attempt

Critique: Suicide risk is inherent in both unipolar and bipolar depression. Antidepressant treatment may confer increased risk in some patients, particularly during the first few weeks of therapy. Appropriate initial and repeat assessment is indicated in the acute phase of treatment, even when a patient has previously agreed to a "no harm" contract. Suicide risk is greatest during the months of April-June. Risk factors for a suicide attempt include the following: * the presence of a psychiatric disorder (e.g., major depression or bipolar depression) * comorbid substance use disorder * active suicidal ideation or plans * a previous attempt (especially one involving high lethality) * a family history of suicide (particularly first degree relatives) * childhood traumaphysical illness comorbidity (e.g., CNS disease, malignancy) * lack of social support * domestic violence * a recent stressful life event * hopelessnessimpulsivity

Which one of the following ethnic groups is considered to be at the highest risk for major depression? Asians African-Americans Hispanics Native Americans Non-Hispanic whites

Critique: The National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) found that Native Americans had an increased relative risk of major depression compared to non-Hispanic whites. This survey also found that being Asian, Hispanic, or African-American reduced the risk (level of evidence 2).

Which one of the following does the U.S. Preventive Services Task Force currently recommend with regard to depression screening in adults? No recommendation either for or against routine screening for depression in primary care Screening only for adults with risk factors for depression, such as a positive family history, or when there is clinical suspicion Screening only when adequate systems are in place to ensure accurate diagnosis, effective treatment, and follow-up Screening in all primary care practices because it is highly effective

Critique: The U.S. Preventive Services Task Force (USPSTF) released revised recommendations for depression screening in 2002. These recommendations reflected new evidence suggesting that screening for depression is beneficial, but only when combined with systems that ensure adequate treatment and follow-up (USPSTF B recommendation). In 2009, the USPSTF updated the guideline by specifically stipulating that staff-assisted depression care supports (such as case management or mental health specialist involvement) needed to be in place to assure accurate diagnosis, effective treatment, and follow-up (USPSTF B recommendation). In 2015 the USPSTF modified its recommendations for screening in adult patients by specifically including pregnant and postpartum women and substituting the phrase "adequate systems" in place of "staff-assisted supports" (USPSTF B recommendation). The USPSTF found insufficient evidence to recommend a specific screening interval (USPSTF I recommendation). Screening adults only when there are risk factors or clinical suspicion was not a recommendation. The recommendations for adolescents (aged 12-18 years) were also updated, and the USPSTF now recommends that screening be performed in this age group when systems are in place to assure accurate diagnosis, psychotherapy (cognitive, behavioral, or interpersonal), and follow-up (USPSTF B recommendation). The USPSTF found insufficient evidence to recommend for or against screening for depression in children 7-11 years of age (USPSTF I recommendation).

Which one of the following best describes bipolar II disorder? A history of one or more periods of impairing manic symptoms that lasted at least 4 days Recurrent periods of major depression with at least one episode of hypomania Alternating periods of hypomania and minor depression A history of at least one episode of acute mania Recurrent major depression refractory to adequate trials of at least three antidepressants from different pharmacologic classes

Critique: The essential feature of bipolar II disorder is a clinical course that is characterized by the occurrence of one or more major depressive episodes (criterion A) accompanied by at least one hypomanic episode (criterion B). The requirement that a hypomanic episode have a duration of at least 4 days is controversial. Data suggests that the mean modal duration of hypomania in patients with bipolar II disorder is 1-3 days, making the DSM-IV-TR definition specific but relatively insensitive. Future editions of the DSM may revise this requirement to reflect current research.

You are considering starting a program in which you screen all pregnant women for depression during their pregnancy and then immediately after delivery. Which of the following should be taken into account in such a program? (Mark all that are true.) The onset of postpartum depression frequently occurs before the patient is seen for a routine 6-week postpartum visit Screening questionnaires for depression during pregnancy have low sensitivity and high specificity The "baby blues" are so common during the first few weeks after delivery that screening for postpartum depression during that time would not be effective Significant dysphoria that arises more than 2 weeks after delivery should raise a strong suspicion for depression "Baby blues" commonly persist for several weeks after delivery

Critique: The fundamental determinant of the effective detection of postpartum depression is awareness by the physician that the onset often occurs within 3-4 weeks of delivery, before the usual time of the postpartum evaluation. For this reason, many screening and detection programs focus on the clinician providing newborn care, who may see the mother more frequently during that window of opportunity. "Baby blues" are transient and mild. Persistence of severe dysphoria, emotional lability, and other typical signs of major depressive disorder beyond a few days, or certainly 1 or 2 weeks, should raise suspicions for postpartum depression. Screening programs generally follow the same principles as those for depression screening in other populations, namely that questionnaires are relatively sensitive but not very specific, leading to a high rate of false-positive results. For this reason, broad-based screening is generally not as effective as targeted case finding in high-risk populations, particularly women with a previous history of major depressive disorder of any sort, postpartum or otherwise.

A thin, 59-year-old postmenopausal Asian female sees you for a routine annual visit. Her past medical history is notable for several episodes of major depression requiring chronic use of an antidepressant for the past decade. She also has a 1-pack/day smoking history. Her family history is positive for major depression in her sister and osteoporosis in her mother. Which of the following antidepressants would add to her osteoporosis risk? (Mark all that are true.) Mirtazapine (Remeron) Imipramine (Tofranil) Fluoxetine (Prozac) Bupropion (Wellbutrin) Duloxetine (Cymbalta)

Critique: The possibility that SSRIs may affect bone metabolism was first raised when functional serotonin receptors and the serotonin transporter were found in osteoblasts, osteoclasts, and osteocytes. Clinical studies have since been published that demonstrate an association between SSRI use and loss of bone mineral density in both men and women (level of evidence 2). A prospective cohort study of 2722 older women found that use of SSRIs (but not tricyclic antidepressants) was associated with an increased rate of bone loss at the hip. In a prospective cohort study of 5008 adults 50 years and older, daily SSRI use was found to be associated with a twofold increased risk of clinical fragility fracture. In a cross-sectional analysis, femoral neck and lumbar spine bone mineral density measurements were significantly lower among men using SSRIs compared with men taking no medications or a non-SSRI antidepressant. Based on these and other studies, the American Psychiatric Association recommends, if clinically indicated, bone mineral density monitoring and adding specific treatment to reduce bone loss in patients taking SSRIs (SOR B).

Compared to the general population, a higher risk for depression is seen in patients following which of the following events? (Mark all that are true.) Acute myocardial infarction Hospitalization for unstable angina Hospitalization for heart failure Cardiac valve surgery Diagnosis of stable angina

Critique: When compared to the general population, the prevalence of depression is three times higher in patients who have recently had an acute myocardial infarction. Prevalence estimates in patients hospitalized for unstable angina, coronary bypass surgery, angioplasty, and valve surgery are similar to those with acute myocardial infarction, and the prevalence is slightly higher in patients hospitalized for heart failure. A higher risk for depression has also been observed among people with coronary heart disease living in the community compared to individuals without coronary heart disease (level of evidence 2).

A 72-year-old male with a history of Parkinson's disease is diagnosed with major depression. His past medical history includes both hypertension and hypercholesterolemia. His current medications are carbidopa/levodopa (Sinemet), 25/250 mg three times daily; hydrochlorothiazide, 25 mg daily; and lovastatin (Mevacor), 40 mg/day. A physical examination is notable for a pill-rolling tremor at rest, mask-like facies, bradykinesia, and mild cogwheel rigidity of the upper extremities. Which of the following antidepressants would be appropriate for this patient? (Mark all that are true.) Citalopram (Celexa) Bupropion (Wellbutrin) Duloxetine (Cymbalta) Amoxapine Venlafaxine

Critique: The presence of Parkinson's disease is an important risk factor for major depression. Major depressive disorder may be present to some degree in up to 40%-50% of patients. Although all antidepressants appear equally effective for patients with Parkinson's disease, SNRIs such as venlafaxine, duloxetine, or desvenlafaxine, as well as noradrenergic agents such as desipramine, are preferred (SOR C). Amoxapine, a tetracyclic antidepressant, has dopamine-receptor blocking properties and the potential for causing a worsening of Parkinson's symptoms. Serotonin-enhancing agents such as SSRIs are associated with a higher risk for exacerbating symptoms, including increases in "off" time and worsening of the tremor. Although the agonistic action of bupropion on the dopaminergic system might be expected to improve the symptoms of Parkinson's disease, this potential benefit is offset by a tendency to induce psychotic symptoms in some patients.

A 38-year-old male presents with panic attacks, and asks for refills of alprazolam (Xanax) prescribed by another physician. Previous treatment attempts with SSRIs approved for panic disorder have not been helpful, often triggering severe agitation and insomnia. Additional history taking reveals that he began to have problems with anxiety in late childhood. He has had a number of impairing depressive episodes and these demonstrate a marked seasonal pattern with increased severity during the winter months. His mother was hospitalized on at least one occasion for a psychotic mania. You continue to explore the patient's history. If found, which one of the following would be most specific for confirming your suspicions of bipolar disorder? Symptomatic improvement on divalproex (Depakote) A full sibling with a confirmed diagnosis of bipolar I disorder A first degree relative with mania responsive to lithium A hypomanic episode

Critique: The presence of manic or hypomanic episodes confirms bipolar disorder. Either a first degree relative with a formal diagnosis of bipolar disorder or a clear response to lithium or divalproex would be considered supportive evidence for a bipolar spectrum illness. Treatment resistance to antidepressants and the induction of mixed states characterized by worsening anxiety, insomnia, and agitation may also be seen. Seasonality is not uncommon in bipolar illness. Comorbidity with anxiety disorders is also common, including generalized anxiety disorder, panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder, and social phobia.

You have made a diagnosis of severe depression in a 30-year-old female who is early in the third trimester of her first pregnancy. Which of the following would be accurate advice regarding the risk of taking antidepressants during the remainder of her pregnancy? (Mark all that are true.) If she takes an SSRI, her baby might develop a syndrome consisting of irritability, abnormal crying, tachypnea, thermal instability, and poor muscle tone If she takes an SSRI her baby is likely to be slightly larger than babies born to mothers who did not take antidepressants She should stop any antidepressant a few weeks before her anticipated due date to prevent a neonatal withdrawal syndrome There is a small but significant risk of a withdrawal syndrome in newborns if serotonergic antidepressants are taken during the third trimester of pregnancy SSRI use in the third trimester has been linked to the development of persistent pulmonary hypertension of the newborn

Critique: The primary adverse effect of antidepressant use in pregnancy, particularly in the third trimester, is a behavioral withdrawal syndrome that occurs roughly two to three times as often in newborns of mothers treated with antidepressants compared to infants of mothers not taking antidepressants. The absolute incidence is small, however, perhaps 5%-10%. The behavioral syndrome consists of irritability, jitteriness, poor feeding, abnormal crying, and poor muscle tone, and is usually mild and transient, with no long-term ill effects. The decision to use an antidepressant in a pregnant woman is based primarily upon the severity of her depression, her desire to treat her depression with medication, and an assessment of the potential harm to the newborn if a severely depressed mother is not effectively treated to remission. If there is strong benefit from treatment, stopping the antidepressant before delivery is not appropriate because the withdrawal syndrome is mild and transient. Maternal use of SSRIs in late pregnancy has been linked to the possible development of persistent pulmonary hypertension of the newborn.

A 32-year-old male who was successfully treated for major depressive disorder with paroxetine (Paxil) for the past 10 months chooses to stop his medication. Within a week he develops symptoms of dysphoria, fatigue, difficulty concentrating, anxiety, and insomnia. In addition, he also complains of an "electric shock" sensation in his legs and "rushing sensations" in his head. Which one of the following is the most likely diagnosis? Recurrence of major depressive disorder Dysthymic disorder SSRI discontinuation syndrome Bipolar disorder

Critique: The symptoms of antidepressant discontinuation syndrome share many features of major depression, including dysphoria, appetite disturbances, sleep problems, fatigue, and difficulty concentrating. Symptoms more characteristic of the SSRI discontinuation syndrome include dizziness, "electric shock" sensations in the face and extremities, "rushing sensations" in the head, headache, and nausea. A rapid reversal of symptoms within a few days of restarting the medication confirms the diagnosis.

After a complete evaluation of a 76-year-old female with depression, you decide she needs to be treated. Her depression is moderately severe, and she has no other significant medical problems.True statements regarding her treatment include which of the following? (Mark all that are true.) In mild to moderate depression, the effectiveness of antidepressant medication is roughly equal to that of short-term, focused psychologic therapies Serotonergic antidepressants are significantly more effective than tricyclic antidepressants for moderate to severe major depression In general, tricyclic antidepressants have a higher dropout rate than serotonergic agents Tricyclic antidepressants should generally not be used in elderly patients because of the higher side-effect related dropout rate compared to serotonergic agents Newer serotonergic agents should generally be avoided in the elderly because of the risk of drug interactions with the many medications usually taken by elderly patient

Critique: The treatment of older patients with depression is not dramatically different than that of younger patients. Psychologic therapy, such as cognitive-behavioral therapy, and antidepressant medication are roughly equally effective in mild to moderate depression, but a combination of both is recommended for severe depression. Elderly patients do not respond better to psychologic therapies than younger patients, and some may even be less responsive. While serotonergic antidepressants are often thought to be more effective than tricyclic antidepressants, evidence suggests they are equally effective. Overall, patients tend to discontinue SSRIs less often than TCAs or heterocyclic antidepressants, but a Cochrane systematic review found the difference is relatively modest. However, in older patients, tricyclic antidepressants have significant side effects such as urinary retention and orthostatic hypotension that cause them to be stopped more frequently. The risk of drug-drug interactions is no greater for serotonergic agents than for other classes of medications, but as with all medications, this should always be considered in elderly patients.

True statements regarding monoamine oxidase inhibitors (MAOIs) include which of the following? (Mark all that are true.) MAOIs are more effective than SSRIs for patients with typical symptoms of major depression (insomnia, decreased appetite) MAOIs may be more effective than tricyclic antidepressants in patients with atypical symptoms of major depression (hypersomnia, increased appetite) MAOIs may precipitate hypertensive crisis when combined with certain foods or medications MAOIs are safe to use in combination with SSRIs

Critique: There have been at least two systematic reviews comparing monoamine oxidase inhibitors (MAOIs) with other antidepressants. One found no significant difference in overall effectiveness between tricyclic antidepressants (TCAs) and MAOIs. The second found that MAOIs were less effective than TCAs in patients between the ages of 18 and 80 with severe depressive disorders, but that MAOIs may be more effective in those with major depression and atypical symptoms, including hypersomnia and increased appetite. MAOIs can trigger serious and sometimes fatal hypertensive reactions when combined with certain medications (e.g., SSRIs, meperidine) and tyramine-rich foods such as preserved cheeses and red wines.

Possible mechanisms implicated in the relationship between depression and increased cardiovascular morbidity and mortality include which of the following? (Mark all that are true.) Increased heart rate variability Increased ratio of parasympathetic to sympathetic tone Abnormalities in platelet aggregation Cardiac rhythm disturbances Reduced compliance with medical recommendations

Critique: There is an interaction between depression and coronary artery disease morbidity and mortality. There have been a number of biologic mechanisms proposed to explain this interaction: * nervous system activation characterized by decreased vagal and increased sympathetic tone, which may predispose to arrythmias * reduced heart rate variability * abnormalities in platelet reactivity * systemic and localized inflammation * underlying stress that leads to the development of both of these disorders. Depression's adverse effect on lifestyle and behavior also likely plays a role; studies have shown reduced adherence to risk-reducing medical recommendations.

A 36-year-old female consults you because of a depressed mood, trouble sleeping, and decreased appetite for 3 weeks. She has no previous history of depression, but her mother is being treated successfully for depression, and urged her to see you. The patient is in a supportive marriage and is functioning well at work. She denies anhedonia, guilt, psychomotor retardation or agitation, trouble concentrating, decreased energy, and suicidal thoughts. Appropriate management options at this time include which of the following? (Mark all that are true.) Sertraline (Zoloft) Paroxetine (Paxil) Cognitive-behavioral therapy Observation only

Critique: This patient has minor, or subsyndromal, depression, meeting only three of nine DSM-IV depression criteria. At the current time, there is no consistent evidence that structured psychotherapy or antidepressants provide significant benefit to patients with minor depression; however, clinical follow-up is warranted to be sure that symptoms do not progress to a major depressive episode.

A 28-year-old business executive presents with a 2-month history of excessive fatigue, feeling hopeless, and being "down in the dumps." She reports that her symptoms have caused her to make careless errors at work and to no longer go out on the weekend with friends. Other symptoms include excessive sleepiness, weight gain, and feelings of failure. Upon further questioning, she recalls a 4-day episode during her late teens during which she inexplicably became elated and restless, went a few days without sleep, quit her job, went on a shopping spree and spent thousands of dollars, and got into fights with family and friends. Which one of the following agents is FDA-approved for treating her depression? Lithium Bupropion (Wellbutrin) Paroxetine (Paxil) Quetiapine (Seroquel) Desipramine (Norpramin)

Critique: This patient likely has bipolar depression. In addition to her current complaint, which meets the criteria for major depressive disorder, the description of the incident in her late teens satisfies DSM-5 criteria for a hypomanic episode. Although there are 10 FDA-approved agents for acute mania, only quetiapine, lurasidone, and a combination of olanzapine and fluoxetine are FDA-approved for bipolar depression. Other FDA-approved antidepressants are indicated only for unipolar depression. While some evidence shows that antidepressants may reduce the risk of recurrent depression in patients with bipolar disorder, they also appear to increase the risk of a switch to a hypomanic or manic episode. Lithium is FDA approved only for the treatment of mania and as maintenance therapy for bipolar disorder. Lamotrigine, an antiepileptic drug, is FDA approved for maintenance therapy of bipolar disorder. Although studies support its use for bipolar depression, it is not currently FDA approved for this indication.

You are considering starting a depression disease management program in your practice. According to the literature, components of successful depression disease management programs include which of the following? (Mark all that are true.) A system to track patients with depression Patient education strategies The use of nurses or other care coordinators to help maintain contact with and educate patients Collaboration with mental health professionals Screening all adult patients in the practice for major depression at least once every 5 years

Critique: Traditional CME lectures and simple dissemination of guidelines have not been shown to improve practice or patient-oriented outcomes. Complex, combination interventions are usually required to affect practice- and patient-level outcomes. Interventions that can improve outcomes in depressed patients include a system to track patients with depression, sometimes called a "disease registry" or a "patient registry"; use of nurses or other trained health professionals to perform patient follow-up, often by phone; interactive clinician education; and a collaborative working relationship with mental health professionals. Having mental health services and primary care in the same location may be helpful, but is not proven to be superior to intermittent case consultations between primary care providers, care managers, and mental health professionals. While the U.S. Preventive Services Task Force has recommended routine screening of all adults for depression at least once, they do not specify an interval for repeat screening.

TCAs (tricyclic antidepressants)

GAD (all TCAs) Bulimia Nervosa (amitriptyline, imipramine, desipramine) Panic disorder (imipramine, clomipramine) Premenstrual dysphoric disorder (clopramine) PTSD (amitriptyline, imipramine) Social anxiety disorder (imipramine) Chronic pain (all TCAs) Headache (amitriptyline, imipramine) Fibromyalgia (amitriptyline) IBS (amitriptyline) Nicotine dependence (nortriptyline) Nocturnal enuresis (nortriptyline) Amitriptyline (Elavil) Clomipramine (Anafranil) Desipramine (Norpramin) Imipramine (Tofranil) Nortripptyline (Pamelor)

MDD (major depressive disorder)

Management

DEPRESSION

Pathophysiology, Epidemiology, and Risk Factors

Depression

Screening and Diagnosis

MAOIs

monoamine oxidase inhibitors; increase serotonin and norepinephrine at the synaptic cleft by inhibiting the enzyme monoamine oxidase which breaks down serotonin and NE--less enzyme, more neurotransmitter, less depression; dangerous; parnate (brand name), Tranylcypromine (generic name) nardil (brand name), aka Phenelzine (generic name) Emsam (brand name), aka Selegiline (generic name); dry mouth, blurred vision, urinary retention, orthostatic hypotension--no tyramines (cheese, wine, etc): could produce hypertensive crisis