Medications for Mood
Vilazodone (Viibryd)
- for mania and major depression -Not recommended to be used with MAOIs, SSRIS, SNRIs, Buspirone -Increased bleeding with ASA, NSAIDS, warfarin (need to monitor) and other anticoagulants
Venlafaxine (Effexor) side effects
-"Side-effexor" has many SE -raises blood pressure (another drug in its class is Sibutramine (Meridia) which blocks dopamine and functions as an anorexic agent- antiobesity medication and also causes increase in blood pressure -causes muscarinic SE like dry mouth, dizziness, constipation
Response time of SSRIs
-2-4 weeks to begin to alleviate sx of depression (just like other antidepressant treatments)
How long should you continue SSRIs until a pt is considered treatment refractory?
-6-8 weeks before you can say pt is nonresponsive to tx
Topiramate (Topamax)
-Adjunctive treatment of seizures -Also effective in mood disorders and bipolar disorders -Used in treatment-resistant unipolar depression -Can markedly reduce appetite -Also used for the treatment of obesity, binge eating, and migraine prophylaxis -"Dope-a-max" -Patients often complain of feeling mentally foggy (trouble thinking, forming sentences, spelling) -used for depression, migraine prophylaxis, seizures, but not so much bipolar. -bad SE -reduces appetite
Teratogenic effects
-All SSRIs are pregnancy category C & should be avoided in pregnancy if possible -The impact of a severe untreated depressive disorder on the mother & fetus must be considered -possible link between exposure to paroxetine (Paxil) in the first trimester and an increased risk of cardiac birth defects
Tetracyclic Antidepressants
-Amoxapine (Asendin) -Maprotiline (Ludiomil)
Restlessness
-An akathisia-like syndrome has been reported primarily with Prozac (fluoxetine) and it can be treated by reducing the dose of the SSRI -The agitation with this syndrome can be profound and often requires discontinuation of the medication
MAOIs
-Avoid Demerol and Fentanyl in patients taking these agents - may cause DEATH!!! -Phenelzine (Nardil) -Tranylcypromine (Parnate) -Isocarboxazid (Marplan)
Paroxetine (Paxil)
-Beneficial cardiac profile; sedating- helps anxious depressed elderly patient -More weight gain
Miscellaneous antidepressants
-Buproprion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban)
Lithium divided doses
-Commonly given in divided doses -Therapeutic response may take up to 4-6 weeks -Pregnancy category D -Increased incidence of birth defects especially Ebstein's anomaly
Amoxapine (Asendin)
-Depressive disorder, esp. major depression with psychosis -Hyperprolactinemia is associated with this drug
Maprotiline (Ludiomil)
-Depressive disorders -Associated with higher rates of seizures, arrhythmias, and fatality in overdose -Do not use in patients with a history of seizures
Potential toxicity
-Desipramine (a TCA), when given with an SSRI such as fluoxetine (Prozac), can have elevated plasma levels up to 400%, with subsequent increased sedation, anticholinergic effect, tremors and potential increased risk of seizures or cardiotoxicity. -SSRIs can also increase levels of warfarin, so prothrombin times should be monitored
Carbamazepine (Tegretol) cont 2
-Drug is associated with a benign and often transient decrease in the WBC count -Can cause agranulocytosis and aplastic anemia -CBC should be done every 2 weeks for the 1st 2 months and quarterly thereafter -Need to educate the patient about signs and symptoms of a developing hematologic problem -This medication is also used to treat diabetes insipidus -Has a vasopressin-like effect on the vasopressin receptor and sometimes causes the development of water intoxication or hyponatremia, particularly in the elderly -can cause water imbalance in the elderly -can cause rash that looks like lupus -can cause false positive pregnancy test
Carbamazepine (Tegretol) cont 3
-Drug may also cause increases in several hepatic enzymes as well as decreased AV conduction -Contraindicated in patients with AV heart blocks -May cause a rash, or rarely, a lupus-like disorder
Lamotrigine (Lamictal)
-Efficacy in the treatment of bipolar depression as an adjunctive agent on monotherapy -can increase dose over time
EPS
-Extrapyramidal symptoms (EPS) -A group of side effects associated with antipsychotic medications. EPS include parkinsonism, akathisia, dystonia, and tardive dyskinesia
Gabapentin (Neurontin)
-FDA approved for the adjunctive treatment of potential seizures and mood disorders -Neurontin will not work for bipolar patients -Used in treatment-resistant unipolar depression -Also helpful in the treatment of chronic pain -Pregnancy category C -The most common side effects are somnolence, fatigue, ataxia, nausea, vomiting and dizziness -may be added with mood disorders, but not usually with bipolar.
Lithium carbonate (Eskalith, Lithonate), slow release lithium carbonate (Eskalith CR)
-FDA approved for the treatment of the acute manic phase of bipolar disorder, as well as maintenance treatment of bipolar disorder -MOA unknown -Lithium is the first line drug in the treatment of bipolar disorder, although some clinicians prefer Valproate -Screening exams to monitor the effects of lithium -Basic chemistry panel, TFTs, CBC, and EKG -Pregnancy needs to be excluded
MAOI diet
-Foods to be avoid: BEER and WINE, soy sauce, sauerkraut, aged chicken or beef live, aged cheese, fava beans, air-dried sausage or other meats, pickles or cured meat or fish, overripe fruit, canned figs, raisins, avocados, yogurt, sour cream, meat tenderizer, yeast extracts, caviar, and shrimp paste -Must discontinue MAOIs 14 days before surgery to prevent hypertensive crisis from anesthesia
Lithium common side effects
-GI distress, weight gain, fine tremor, cognitive impairment ("fuzzy thinking"), polyuria, hypothyroidism -Symptoms of lithium toxicity include nausea, vomiting, diarrhea, coarse tremor, ataxia, H/A, slurred speech, confusions, arrhythmias -Many drug interactions -trouble forming thoughts -can gain a lot of weight! -tremor -causes hypothyroidism -must monitor levels; can become lithium toxic
Most common SSRI serotonergic side effect - GI effects
-GI effects (N/V) -give SSRIs with food! -nausea usually improves in the first few days of tx -decreased appetite is common early in treatment bc of the nausea but will usually improve in a few days -headaches (usually transient) -Prozac and Zoloft can cause insomnia (good for pts with atypical depression who sleep all the time) -Paxil is sedating (good for anxiety)
OCD and bulimia require
-HIGHER doses of SSRIs -while high doses may be necessary in some pts, many will respond to standard dosing AFTER 6-12 weeks -60-80mg of fluoxetine (Prozac) or 200-300mg of sertraline (Zoloft) -when >40mg a day of fluoxetine (Prozac) is given, dosage should be divided into 2 doses to minimize SE like anxiety
TCA adverse drug reactions continued
-Histaminic blockade can produce sedation and weight gain -Many of these agents should be given at bedtime to prevent excess daytime sedation -These drugs slow cardiac conduction, leading the IV conduction delays, prolonged PR and OT interval, AV block, and t-wave flattening -Seizures can occur with these drugs -May produce tremors and ataxia -In overdose agitation, delirium, seizures, coma, and death may occur -Erectile and ejaculatory dysfunctions may occur in males and anorgasmia may occur in females
Panic disorder pts require
-LOWER doses of SSRIs to prevent exacerbation of anxiety in initial weeks of treatment -12.5-25mg of sertraline (Zoloft), 10mg of paroxetine (Paxil), or 5mg fluoxetine (Prozac) -after one week, dosage may be increased gradually to standard doses
Mirtazapine (Remeron) cont
-Lacks annoying anticholinergic side-effects of the tricyclics -Little effect on sexual functioning -Some effect in anxiety disorders -Sedation is the most common side effect, usually decreased over time (occurs in more than 50% of patients) -Increase in appetite and weight gain is common! -Can potentate the sedation of alcohol and benzodiazepines
Mood stabilizers
-Lithium carbonate (Eskalith, Lithonate), slow release lithium carbonate (Eskalith CR)
Fluoxetine (Prozac, Sarafem) Review
-Low overdose harm; treats OCD; may treat pain disorder, chronic pain syndromes, substance abuse -Weight loss and anorexia
Anesthesia for ECT
-Need anesthesia when performing -Brevital is a barbiturate that is very useful since it is short acting and caused less post-ictal arrhythmias than Pentothal
Lithium Pregnancy D
-Need thyroid function tests, CBC, EKG, make sure not pregnant. -Lithium is category D, causing birth defects. Ebstein's anomaly is a rare congenital heart defect in which parts of the tricuspid valve are abnormal. (Right ventricle goes up into right atria).
Paroxetine (Paxil) clinical guidelines
-Paroxetine should be taken at bedtime because of the sedative properties!! -Patient may have a reduction in anxiety early in treatment due to sedating properties -Relatively safe in overdose -Patients may require bid dosing in dosages above 40 mg per day -Paxil CR at a dosage of 37.5mg is bioequivalent to 30mg of immediate-release Paxil
Which SSRIs may cause sedation?
-SSRIs are less sedating than TCAs, but sedation can occur with paroxetine (Paxil) or fluvoxamine (Luvox) -if this occurs, give the SSRI at bedtime
SSRI overdose
-SSRIs are much safer in overdose than other antidepressants (like TCAs or MAOIs which can be lethal)
SSRIs are better tolerated than TCAs or MAOIs. What else?
-SSRIs don't cause orthostatic hypotension bc they don't block alpha-1 adrenergic receptors (like TCAs do) -SSRI's produce less sedation and weight gain than TCAs or MAOIs bc of minimal effect on histamine receptors -SSRI's have minimal effect on muscarinic cholinergic receptors (thus, no dry mouth, constipation, blurred vision, urinary retention) -SSRI's have a lower rate of seizures than TCAs
Nortriptyline (Pamelor, Aventyl)
-Same indications as Desipramine (Norpramin) -qhs, inc over 1-4 weeks -Widely used in the treatment of chronic pain -Among the least likely TCA to cause orthostatic hypotension
Carbamazepine (Tegretol) cont
-Screening labs to monitor the effects: CBC, EKG, basic chemistry panel -Should not be given to patients with preexisting liver, cardiac, or hematological diseases -not recommended for patients with renal dysfunction because it has active metabolites that are renal excreted -Pregnancy category C so get pregnancy test! -Absorption is enhanced when the drug is taken with meals -must follow CBC bc it tends to trend down -need bloodwork done every 2 weeks for first 2 months, then quarterly
Depakene (Valproic Acid, Sodium Valproate) and Depakote (Divalproex) cont
-Screening tests should be ordered including basic chemistry panel, CBC and EKG in patients over 40 or with preexisting cardiac disease -Pregnancy should be excluded (Cat D)!!!! -Cause increased incidence of neural tube defects (bc it messes up folic acid absorption) -Can cause clotting disorders and hepatic failure in infants -Should not be given to patients with liver disease -Many drug interactions
SNRI's
-Serotonin and Norepinephrine reuptake inhibitors -Duloxetine (Cymbalta)
SSRIs
-Serotonin-Specific Reuptake Inhibitors -Most widely prescribed class of antidepressants
Setraline (Zoloft)
-Shorter half life (1 day, not 2) -Less agitation but more diarrhea
SSRIs are generally better tolerated than...
-TCA's and MAOIs -SSRIs also have significantly less effect on muscarinic, histaminic, and adrenergic receptors -SSRIs have few SE and are often once a day dosing
combination of Bupropion and fluoxetine (Prozac)
-The combination of Bupropion and fluoxetine (Prozac) is one of the most effective and well-tolerated treatments for all types of depression -But may exacerbate panic disorder -Bupropion may give a false-positive result on urinary amphetamine screens (urine drug test)
Depakene (Valproic Acid, Sodium Valproate) and Depakote (Divalproex)
-The only anticonvulsant FDA approved in the treatment of bipolar disorder -Also use in schizoaffective disorder -More effective in rapid cycling and mixed episode than lithium -Useful in schizophrenia if inadequate response to antipsychotics -Helpful in impulse control disorders
TCA overdose
-These agents are extremely toxic in overdose -Overdose from as little as 1-2 grams may cause DEATH -As small as a 10 day dose or less can be lethal -Death usually occurs from cardiac arrhythmia's, seizures, or severe hypotension -Overdose should be treated with gastric lavage, activated charcoal, cardiac monitoring and supportive therapy -never give a month's worth of medication of TCAs to depressed pts. Give at most a week's worth.
Carbamazepine (Equetro)
-Time released preparation of Tegretol -FDA approved treatment for bipolar disorder
Carbamazepine (Tegretol) lab interferences
-Transient decrease in thyroid hormones (T4, T3) and increase in TSH -Increase in serum cholesterol by increases HDL -May interfere with dexamethasone- suppression test -May cause false-positive pregnancy tests
Atypical antipsychotics
-Unique compounds that are chemically unrelated to the SSRIs, TCA's and MAOIs -Often used to treat bipolar disorder and mania -They require the same amount of time to achieve clinical efficacy -These antidepressants are contraindicated for two weeks before or after the use of an MAOI
Oxcarbazepine (Trileptal)
-Used for mood disorders and bipolar disorder -May be as effective as carbamazepine for bipolar and better tolerated -Starting dose is 300mg bid, increase by 600mg each week to maintenance dose of 1200-1400 mg/day
Pregabalin (Lyrica)
-Used in general anxiety disorder and fibromyalgia -Little evidence to support its use in bipolar disorder
Anticonvulsants
-Useful in bipolar patients that have failed a drug trial of lithium -Also used in schizoaffective disorder, treatment of resistive depressive disorder, schizophrenia, impulse control disorders, borderline personality disorders, and behavioral disturbances associated with developmental disability
Pregnant and nursing women
-avoid administering any drug to a woman who is pregnant (especially 1st trimester) or is breastfeeding -This rule is broken if her mental condition is severe and the benefit outweighs the risk -The two most teratogenic psych drugs are lithium and anticonvulsants -Lithium is associated with birth defects, especially Ebstein's anomaly -Anticonvulsants are associated with neural tube defects and craniofacial abnormalities (Reduce risk with folic acid)
SSRI pharmacology
-block serotonin reuptake into presynaptic nerve terminals -this leads to enhanced serotonergic neurotransmission -half life is 24 hrs for all except fluoxetine (Prozac) -takes about 5 days to reach steady-state plasma concentration
Selegiline (EmSam)
-bypasses the gut -is a transdermal patch -Advantage of a transdermal administration of an MAOI is that it bypasses the gut, tyramine pressor effects are mitigated and dietary restrictions are generally not necessary as they are with oral MAOIs -change patch q24h -can be activating in some patients because selegiline is metabolized to amphetamine-like metabolites
Trazodone (Desyrel)
-commonly prescribed for insomnia!! -approved for depressive disorders -It is used clinically to reduce anxiety and decrease agitation and aggression in elderly demented patients -It is also effective in some patients with chronic pain syndromes -qhs, then increase by 50mg/day as tolerated, may require bid dosing initially -Side effects include orthostatic hypotension, gastric irritation, priapism (known for priapism!)
SSRI drug interactions
-cytochrome P450 enzymes -potential toxicity
Setralline (Zoloft) adverse drug reactions
-cytochrome P450; inhibition of hepatic enzyme may lead to mild elevations of TCAs and antiarrhythmics -SE: diarrhea
In summary, SSRIs...
-don't block alpha-1 receptors -have a minimal effect on histamine and cholinergic receptors -have a lower rate of seizures
Increased risk of suicidiality is probably greatest during...
-early stages of treatment or with a change in dose -make phone contact within a few days of initiating an antidepressant or changing the dose -then, see the pt within a week and at least every 1-2 weeks until pt is stabilized
TCA adverse drug reactions
-elderly are extremely sensitive to these meds. Start on very low dose! -most side effects of TCA's are dose related -elderly patient are much more sensitive to the side effects, and they may be unable to tolerate therapeutic dosages -cholinergic blockage may produce dry mouth, blurry vision, constipation, urinary retention, heat intolerance, tachycardia, and exacerbation of narrow angle glaucoma -constipation may be alleviated by stool softeners -dry mouth can be improved with the use of sugarless candy -alpha-1-adrenergic receptor blockade can lead to orthostatic hypotension, resulting in falls -patients should be cautioned to stand up slowly when getting out of bed -dizziness and reflex tachycardia may occur
TCA adverse drug reactions summary
-elderly need very low dose! -give at bedtime to prevent daytime sedation -cholinergic blockage (dry mouth, blurry vision, constipation, urinary retention, heat intolerance, tachycardia, narrow angle glaucoma) -alpha-1 blockade can result in orthostatic hypotension, dizziness, reflex tachycardia -Histaminic blockade can produce sedation and weight gain -slow cardiac conduction -seizures, tremors, ataxia -sexual dysfunction
SSRIs are highly bound to plasma proteins, except for
-escitalopram (Lexapro) -fluvoxamine (Luvox)
SSRIs approved in children
-fluoxetine (Prozac) -sertraline (Zoloft)
Fluoxetine (Prozac, Sarafem) SE
-fluoxetine is more likely to produce anxiety and insomnia than other SSRIs -fluoxetine inhibits liver enzyme cytochrome CYP2D6 -Use caution when combining with a TCA or an antiarrhythmic agent -Can also elevate levels of many neuroleptic agents and lead to dystonia, akathisia, or other extrapyramidal symptoms -Can lead to moderate plasma elevations of some benzodiazepine with increase sedation and psychomotor impairment -Can elevate Carbamazepine and phenytoin levels -Can prevent conversion of codeine to its active metabolite and can prevent pain reduction (prevents conversion to Codeine (bc metabolized in liver P2D6 and P450 and has long half life). Will not allow pt to have relief of pain, like during surgery. Careful when using this with other drugs)
Escitalopram (Lexapro)
-for a variety of depressive and anxiety disorders -can increase dose after one week -maximum dose reserved only for treating refractory pts who have taken it for 4-6 weeks already
Fluvoxamine (Luvox)
-for a variety of depressive and anxiety disorders -can titrate up over several weeks -pts often require BID dosing in doses above 100-200mg per day -Columbine school massacre caused sales to drop
Monoamine Oxidase Inhibitors
-for depression and anxiety disorders -Given the dietary restriction and the risk of hypertensive crisis, most clinicians use MAOIs only after more conventional treatments have failed -PAs don't prescribe MAOIs unless working specifically in psych. Risky to prescribe bc pt must be on very strict diet
Venlafaxine (Effexor and Effexor XR)
-for depression, dysthymia, ADHD, chronic pain management -good in severely depressed pts -faster than usual antidepressants (only 1-2 weeks) -advantages don't occur until high doses
Citalopram (Celexa)
-for depression, dysthymia, OCD, panic disorder -usually given at bedtime -elderly have lower dose (cut in half) -citalopram has low overall effects on P450 enzymes -can increase dose after one week -maximum dose reserved only for treating refractory pts who have taken it for 4-6 weeks already
Desipramine (Norpramin)
-for depressive disorder, anxiety disorders, and chronic pain -qhs, inc over 1-4 weeks -Among the least sedating and least anticholinergic TCA's -It should be considered a first line heterocyclic agent in elderly patients
Trimipramine (Surmontil)
-for depressive disorder, anxiety disorders, and more -qhs, inc over 1-4 weeks -no significant advantage over other TCAs
Imipramine (Tofranil)
-for depressive disorder, anxiety disorders, enuresis, chronic pain, and more -qhs, inc over 1-4 weeks -Imipramine has well documented effectiveness in the treatment of panic disorder -It is also effective in the treatment of enuresis in children
Mirtazapine (Remeron)
-for depressive disorders -MOA: Selective alpha-2-adrenergic antagonist that enhances noradrenergic and serotonergic neurotransmission -qhs, inc dose after several days
Protriptyline (Vivactil)
-for depressive disorders -take in AM!!! -inc over several days to weeks -The least sedating and most activating TCA, avoid giving near bedtime as it can cause insomnia
Clomipramine (Anafranil)
-for depressive disorders, OCD, and more -qhs, increase over 1-4 weeks -Average dose is 150-250 mg/day FDA approved for the treatment of OCD -OCD symptoms may require a longer duration of treatment (2-3 months) to achieve efficacy -This drug may be especially useful in a depressed patient with strong obsessional features -The side effect profile often prevents patient from achieving an adequate dosage -This drug has a higher risk of seizure than other TCA's!! -Unusual side-effect of yawning orgasm! -often causes impotence, ejaculation difficulties in men, but in a few pts can cause yawning orgasms
Doxepin (Adapin, Sinequan)
-for depressive disorders, anxiety disorders, chronic pain, and more -qhs, inc over 1-4 weeks -average dose is 150-250 mg/day -Doxepin may be used in the treatment of chronic pain -It is one of the most sedating TCA's -Its strong antihistamine properties makes it one of the most effective antipruritic agents available -It is useful for insomnia at a lower dosage
Amitriptyline (Elavil, Endep)
-for depressive disorders, anxiety disorders, chronic pain, insomnia, and more -widely used for chronic pain and prophylaxis of migraine headache -qhs -increase dose over 1-4 weeks -Average dose is 150-250 mg/day -Strong anticholinergic effects are often difficult for patients to tolerate -can be useful for insomnia, migraine, chronic pain at a lower dose -high dose to treat depression
Onlanzapine and fluoxetine (Symbyax)
-for depressive episodes in pts with bipolar disorder -(atypicals have less SE than typicals; used for pts with psychotic disorders)
Sarafem
-for females for PMDD (Premenstrual dysphoric disorder) -expensive brand name
Duloxetine (Cymbalta)
-for major depression -for pain associated with diabetic neuropathy, fibromyalgia, and other chronic pain conditions (first antidepressant approved to treat pain conditions like diabetic neuropathy) -off label use for stress incontinence -start at a lower dose and then go up (starting at a higher dose is too activating and associated with high rates of nausea; a gradual titration is well tolerated) -take with food (causes nausea)
Sertraline (Zoloft)
-for major depression, OCD in children and adults, panic disorder, PTSD, PMDD, and more -can increase dose in partial responder pts -as all these drugs, elderly get half as much mg -children under 13yo also get half as much mg -for PMDD, can take throughout cycle or just luteal phase
Fluoxetine (Prozac, Sarafem)
-for major depression, OCD, bulimia, PMDD -can inc dose -weekly dose available!! -good for atypical depression; will lose hunger and weight -split the doses during the day, or else may get anxious -tx of OCD may require higher dose than depression -elderly pts require lower doses and every other day dosing may be used (long half life)
Tricyclic Antidepressants
-for major depression, dysthymia, and depressed phase of bipolar disorder -also have efficacy in anxiety disorder and OCD -useful adjuncts in treating bulimia and chronic pain syndromes -not safe to overdose on these! Extremely lethal in overdose. Many SE and complications
Nefazodone (Serzone)
-for major depression, dysthymia, and the depressed phase of bipolar disorder, anxiety, PMDD, chronic pain, PTSD -start BID, inc dose after several days to weeks -Little or no effect on sexual functioning -Common side effects are nausea, dry mouth, dizziness, sedation, agitation, constipation, weight loss and headache -"son of Trazodone" - highly sedating!!
Buproprion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban)
-for major depression, dysthymia, bipolar depression, SAD, and ADHD in children and adults -Low-dose Bupropion is used adjunctively to treat the sexual dysfunction associated with SSRIs -Helpful in smoking cessation -start BID, then inc to TID after 4-5 days -Slow release - begin with 150 mg qam for 3 days then increase to 150mg bid for SR tabs
Paroxetine (Paxil)
-for major depression, panic disorder, social phobia, OCD, and more -Paxil CR = controlled release -can increase dose if partial response occurs -must take at bedtime bc it makes you tired -SE: polyphagia and weight gain -not at good for pts with atypical depression -but treats both anxiety, panic, depression (kills two birds with one stone)
Desvenlafaxine (Pristiq)
-for major depressive disorder -SNRI -the major active metabolite of venlafaxine (Effexor XR) so less SE (but no real benefit)
MAOI Hypertensive crisis
-from consuming tyramine-containing foods -characterized by markedly elevated blood pressure, headache, sweating, nausea and vomiting, photophobia, autonomic instability, chest pain, cardiac arrhythmias, and even coma and death
fluoxetine (Prozac) half life
-half life is 2-4 days and it's active metabolite has a half-life of 7-10 days -thus it takes over a month to reach steady state plasma concentrations
Carbamazepine (Tegretol)
-helpful for pts with rapid cyclind bipolar disorder -indicated for temporal lobe epilepsy and trigeminal neuralgia -Used for the acute manic phase of bipolar disorder, schizoaffective disorder, bipolar or depressed type and cyclothymia -More effective than lithium in the treatment of rapid cycling and mixed episode -Helpful in some impulse control disorders, the treatment of alcohol withdrawal and benzodiazepine withdrawal
TCA pharmacology
-highly protein bound and lipid soluble -half-lives are >24hrs which allows for once daily dosing -more SE and greater lethality in overdose because of the greater blockade of cholinergic, adrenergic, and histaminic receptors
SSRI SE continued - insomnia
-insomnia is more common with fluoxetine (Prozac) and sertraline (Zoloft) -trazodone 50-100mg qhs may help -give SSRI in morning if insomnia occurs
Fluoxetine (Prozac, Sarafem) clinical guidelines
-long half-life!! -long half-life permits daily dosing and decreased withdrawal symptoms following abrupt discontinuation of meds -relatively safe in overdose -the long half-life requires waiting at least 5 weeks after discontinuation before beginning a MAOI -pts often require BID dosing (40mg morning and 30mg at noon) -later afternoon doses often disrupt sleep
SSRIs proven efficacy in tx of...
-major depression -dysthymia -OCD -panic disorder -bulimia nervosa -PTSD -generalized anxiety disorder -social phobia -premenstrual dysphoric disorder -also effective for bipolar depression (but should be used in conjunction with a mood stabilizer bc can induce mania)
"Level out" with Mood stabilizers
-mood stabilizers are for bipolar disorders -Used for the treatment of mania, depression, & mixed states associated with bipolar disorder & schizoaffective disorder -Also for severe cyclothymia & unipolar depression -Helpful in the treatment of impulse control disorders, severe personality disorders, & behavioral disorders in the developmentally disabled Includes lithium, anticonvulsants, & calcium channel blockers
Plasma concentration of SSRIs vs clinical efficacy
-no correlation -thus, measuring plasma levels is not clinically indicated -pt will not die from overdose of one month's worth of SSRIs
Serotonin syndrome
-occurs when SSRIs are combined with MAOIs -SSRIs should NOT be used for 2 weeks before or after the use of an MAOI -nausea, confusion, hyperthermia, autonomic instability, tremor, myoclonus, rigidity, seizures, coma, death
SSRI dosing
-once a day -don't need to check titers -for most pts, the dosage does not need to be titrated upward -there is no linear relationship between SSRI dose and response -start on lower doses for elderly pts; longer half-life, will stick around longer
SSRIs NOT FDA approved for children
-paroxetine (Paxil) -duloxetine (Cymbalta) -venlafaxine (Effexor) -citalopram (Celexa)
Buproprion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban) side effects
-relatively few SE -however, CANNOT use in pt with eating disorder or seizures bc it inc risk for seizures (lowers seizure threshold) -increases BP in pts who already have HTN -Bupropion has fewer side effect than TCA's and causes less sexual dysfunction than the SSRIs -does not produce weight gain or orthostatic hypotension -Higher likelihood of weight loss then weight gain -This is a good choice for a patient with cardiac disease -Most common side effect are insomnia, CNS stimulation, headache, constipation, dry mouth, nausea, tremor -Avoid this drug in patients with anorexia or bulimia due to possible electrolyte changes, potentiation of seizures -Not recommended during pregnancy or HTN -Seizure risk increases with increased dose -May increase BP in previously hypertensive patients
Other miscellaneous SE of SSRIs
-restlessness -teratogenic effects -breastfeeding
TCA Choice of drug and dosage
-selection should be based on patent's past response to medication, family history or medication response, and side effect profile -dosage should be titrated up over several days to weeks to allow patient to adjust to side effects -therapeutic dose and trial should be given for 3-4 weeks before a patient is considered a non-responder
SSRI discontinuation syndrome
-should always taper SSRIs over several weeks when discontinuing the drug -on discontinuation, some pts may have dizziness, lethargy, nausea, irritability, headache -sx are usually transient and are more likely to occur with short acting agents like paroxetine (Paxil) or fluvoxamine (Luvox) -discontinuing paroxetine may also be complicated by cholinergic rebound symptoms, like diarrhea
SSRIs can cause sexual dysfunction such as decreased libido, delayed ejaculation, anorgasmia. How do you treat this?
-sildenafil (Viagra) one hr before sex -tadalafil (Cialis) -vardenafil (Levitra) one hr before sex -bupropion (Wellbutrin) -buspirone (BuSpar) -mirtazapine (Remeron) or nefazodone (Serzone) one hr before sex
Black box warning for antidepressants in children and adolescents
-suicidal thinking and behavior -prescribers should warn pediatric patients and their parents of the potential risk and carefully monitor for signs of treatment emergent suicidiality -follow up very frequently with kids -telephone often
Miscellaneous side effects of SSRIs
-sweating, anxiety, dizziness, tremors, fatigue, dry mouth -SSRIs, like all other antidepressants, can induce mania or rapid cycling in bipolar pts!
Paroxetine (Paxil) adverse drug rxns
-use caution when combining with TCAs or antiarrhythmics -can also elevate some neuroleptics and inc the incidence of EPS -weight gain is common
ECT
-very effective, little understood -used in major depression, manic episodes, schizophrenia, Bipolar I, major depression not responding to therapy, who cannot tolerate the meds, or who have severe psychotic symptoms or who are acutely suicidal, stuporous, or agitated -Seizure is produced -Memory impairment is common but long term effects are minimal -Back to cognitive baseline in 6 months (Related to amount of electrical stimulation used) -Side effects are headache, confusion, delirium -generally not firstline tx
escitalopram (Lexapro)
10mg
fluoxetine (Prozac), citalopram (Celexa), and paroxetine (Paxil)
20mg [decrease to 10mg for elderly]
sertaline (Zoloft) and fluvoxamine (Luvox)
50mg [decrease to 25mg for elderly]
Atypical antipsychotics examples
Aripiprazole (Abilify) Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon) Asenapine (Saphris) Lurasidone (Latuda) Olanzapine and Fluoxetine (Symbyax)
Substance abuse therapies
Campral (Acamprosate) For maintenance of abstinence of alcohol Subutex (Burenorphine) Opioid abuse Antabuse (Disulfirim) Alcohol deterrent Methadone Opioid abuse Revia (Naltrexone) For maintenance of abstinence of alcohol (don't need to know these!)
Secondary Amine Tricyclic Antidepressant Drugs
Desipramine (Norpramin) Nortriptyline (Pamelor, Aventyl) Protriptyline (Vivactil)
Special note about setraline (Zoloft)'s adverse drug reactions
Lowest overall P450 enzyme effects of all the SSRIs!!!
fluoxetine (Prozac) is used in kids for
MDD and OCD
Lack of response to one SSRI or inability to tolerate the drug is...
NOT predictive of the same reaction to another SSRI. However, ask if the pt's family members have had success with a certain SSRI because pt may have similar success.
sertraline (Zoloft) is used in kids for
OCD only
Combination atypical and SSRI
Onlanzapine and fluoxetine (Symbyax)
Cytochrome P450 enzymes
SSRIs are competitive inhibitors of a variety of cytochrome P450 liver enzymes. This can result in elevated plasma levels of medications metabolized by these enzymes. Elevated plasma levels may lead to toxic side effects. (SSRIs can inc levels of warfarin and desipramine)
Breastfeeding
SSRIs are secreted into breast milk and mothers should not breast feed while taking SSRIs
SSRI and 5HT1a receptor partial agonist
Vilazodone (Viibryd)
For sexual dysfunction, can switch the SSRI antidepressant to
bupropion (Wellbutrin), nefazodone, or mirtazapine
Which SSRI should not be used for 5-6 weeks before or after the use of an MAOI?
fluoxetine (Prozac) because of the long half life
SSRIs have some efficacy in treating...
pain syndromes like migraine HA, chronic pain, impulse control disorders, menopause (tricyclics may be more effective though)