Chapter 14: Antidepressants, Psychomotor Stimulants, and Lithium
Drug interactions of Tricyclic Antidepressants and Phenothiazines
CNS depression, anticholinergic effects
Monoamine Therapy of Mental Depression
theory that mental depression is caused by low brain levels of norepinephrine and serotonin (monoamines)
TCAs
tricyclic antidepressants, a class of antidepressant drugs
Drug interactions of Tricyclic Antidepressants and Barbiturates
Increased metabolism of tricyclics (decreased effectiveness) increased sedation
What does CNS stimulation mean?
Increased wakefulness and alertness. CNS stimulants also raise blood pressure and increase heart rate and breathing rate.
What are some of the clinical uses of psychomotor stimulants?
Psychomotor stimulants are used to treat narcolepsy (uncontrolled tendency to fall asleep) and hyperkinesis in children.
Robyn's physician has just prescribed Nardil for severe depression. What foods does Robyn need to avoid and why?
Robyn needs to avoid wine, beer, herring, and certain cheeses. These contain tyramine, which may produce massive releases of norepinephrine that could result in a hypertensive crisis or cerebral stroke.
What are the main pharmacological differences between the secondary and tertiary amine antidepressants?
Secondary amines mainly increase brain levels of norepinephrine more than serotonin, while the tertiary amines mainly increase brain levels of serotonin more than norepinephrine. Tertiary amines also cause greater sedation.
Which antidepressant drug classes are considered to be the preferred therapy for depression?
The SSRIs are currently considered the preferred drugs for major depression because they have fewer side effects/adverse effects than other antidepressants.
SSRIs
selective serotonin reuptake inhibitors, a class of antidepressant drugs. Also effective in the treatment of most anxiety disorders such as PTSD and OCD.
SNRIs
serotonin and norepinephrine reuptake inhibitors, a class of antidepressant drugs
What are the adverse effects of the selective serotonin reuptake inhibitors?
All the SSRIs gastrointestinal disturbances involve nausea, diarrhea, dry mouth, and anorexia. The most common symptoms of overdosage include confusion, fever, nervousness, tremor agitation, restlessness, and other signs of CNS excitation; seizures also have been reported. Sudden discontinuation of SSRI treatment has been associated with a discontinuation syndrome. Symptoms include dizziness, nausea, insomnia, and anxiety.
The adverse effects of lithium include: A. vomiting B. diarrhea C. increased urination D. ringing in the ears E. all of these
Answer: A
The main pharmacologic effect of the SSRIs is: A. increase levels of norepinephrine B. increase levels of serotonin C. decrease levels of norepinephrine D. decrease levels of serotonin E. decrease levels of dopamine
Answer: B
Which drug requires a dietary restriction for foods containing tyramine? A. nortriptyline B. tranylcypromine C. venlafaxine D. fluoxetine E. methamphetamine
Answer: B
The serotonin syndrome is mainly associated with overdosage of: A. tricyclic antidepressants B. monoamine oxidase inhibitors C. selective serotonin reuptake inhibitors D. psychomotor stimulants E. lithium
Answer: C
Which of these represents the drug that is not correctly matched with its drug classification? A. paroxetine—SSRI B. amitriptyline—TCA C. methylphenidate—MAOI D. duloxetine—SNRI E. phenelzine—MAOI
Answer: C
The main pharmacologic effects of TCAs on neurotransmitter activity is: A. increase norepinephrine B. increase acetylcholine C. increase serotonin D. increase norepinephrine and serotonin only E. increase norepinephrine, acetylcholine, and serotonin
Answer: D
Venlafaxine (Effexor) is classified as: A. MAOI B. TCA C. SSRI D. SNRI E. psychomotor stimulant
Answer: D
Adverse effects of TCAs include: A. liver toxicity B. cardiac arrhythmias C. convulsions D. postural hypotension E. all of these
Answer: E
Clinical uses of bupropion (Wellbutrin) include: A. treatment of depression B. treatment of bipolar disorder C. cessation of smoking D. treatment of obesity E. all of these
Answer: E
The pharmacologic effects of TCAs include: A. alpha-adrenergic blockade B. antihistaminic C. anticholinergic D. sedation E. all of these
Answer: E
Common SSRIs include: (6)
Citalopram (Celexa) 20-60mg dose range, Low CNS activation Escitalopram (Lexapro) 10 - 30mg dose range, Low CNS activation Fluoxetine (Prozac) 20 - 60mg dose range, High CNS activation Fluvoxamine (Luvox) 50 - 300mg dose range, Sedating CNS activation Paroxetine (Paxil) 20 - 60mg dose range, Low CNS activation Sertraline (Zoloft) 25 - 200mg dose range, Low CNS activation
Common SNRIs include: (3)
Desvenlafaxine (Pristiq) 50 - 200mg, Moderate CNS activation Duloxetine (Cymbalta) 40 - 120mg, Low CNS activation Venlafaxine (Effexor) 75 - 375mg, Moderate CNS activation
Drug interactions of Tricyclic Antidepressants and Anticholinergics/Antihistamines
Dry mouth, constipation, urinary retention, blurred vision
Drug interactions of Tricyclic Antidepressants and Amphetamines
Increased CNS stimulation
Drug interactions of Tricyclic Antidepressants and MAO inhibitors
Increased CNS stimulation, hyperpyrexia, seizures
Drug interactions of Tricyclic Antidepressants and SSRIs, SNRIs
Increased CNS stimulation, serotonin syndrome
Janet has just been prescribed lithium for her manic states. What should be included in her medication counseling?
It may take one to two weeks of treatment before noticing any difference. Common side effects include nausea and tremors, but they should diminish with continued treatment. Also, she will have increased thirst and frequency of urination. It is important to have adequate fluid and sodium intake. She should immediately report any excessive nausea, vomiting, CNS stimulation, dizziness, abnormal muscle movements, low blood pressure, or ringing in the ears. It is important to have her blood levels checked as required by her physician.
Explain the Monoamine Theory of Mental Depression
Levels of norepinephrine and serotonin (5HT) in the brain can influence mental behavior. Low levels of norepinephrine and/or serotonin are associated with mental depression while high levels of norepinephrine and/or serotonin may be involved in mania. This concept is know as the Monoamine Theory of Mental Depression.
Explain the mechanism of action and major adverse effects of lithium.
Lithium is referred to as a mood stabilizer and is used to treat individuals who experience wide shifts of mod, mania or alternating cycles of depression and mania (bipolar mood disorder). It interferes with nerve conduction. As a result, there is a decrease in the excitability of nerve tissue. Most patients experience some nausea or tremors. With overdose, vomiting, diarrhea, drowsiness, loss of equilibrium, ringing in the ears, and frequent urination are common. At toxic levels, the heart and kidneys may be damaged, leading to the development of cardiac arrhythmias or nephritis. Lithium occasionally produces disturbances of the thyroid gland. In acute overdoses, muscle fasciculations, convulsions, and circulatory collapse leading to death are possible.
How do the MAO inhibitors increase the levels of norepinephrine and serotonin in the brain?
MAO inhibitors suppress the enzyme MAO, which normally breaks down norepinephrine and serotonin into metabolites that are then excreted by the kidneys. Drugs that inhibit, or block, MAO are called appropriately MAO inhibitors (MAOIs). By inhibiting MAO, these drugs decrease the amounts of norepinephrine and serotonin that are destroyed. Consequently, the amounts of these neurotransmitters increase after MAO inhibition.
What neurotransmitters are deficient in mental disorders?
Norepinephrine and serotonin are the neurotransmitters that are deficient in mental depression.
Joe works as a volunteer on a depression hotline. What type of depression is experienced by each of the following anonymous callers? - Caller A says he has no particular reason to feel down, but he's feeling really depressed anyway. He says he gets down-and-out a lot, but it doesn't usually get quite this bad. He wonders if there's any kind of treatment or drug for how he feels. - Caller B says she's usually a happy-go-lucky sort of person, but she's been feeling depressed since her mother died last month. She thinks she should be over the worst of her grief by now and wonders if she should get counseling. (LO 14.1)
Students' answers should include the following points: Caller A appears to have major depressive disorder (MDD) and may need both drug treatment and psychotherapy to cope effectively with the problem. Caller B appears to have exogenous depression, for which the support of friends and family may be sufficient to alleviate the symptoms.
Assume that one of your duties in the mental health clinic where you work is to note for each patient any contraindications or potential drug interactions for current medications. You also assist with drug overdose emergencies. - Patient A has been diagnosed with major depressive disorder. He's been taking Elavil for several weeks, but it makes him excessively drowsy, so his medication is being changed to an MAO inhibitor. The patient also is taking a prescription decongestant for allergies. What should you note on the patient's chart regarding adverse effects and drug interactions? - Patient B appeared at the clinic suffering from a possible overdose of lithium. She appeared drowsy and complained of dizziness and ringing in her ears. What should be done to help rid her body of the excess lithium?
Students' answers should include the following points: Patient A) Excessive drowsiness is a common side effect of Elavil, which is a tricyclic antidepressant. Elavil can increase the CNS stimulation of MAO inhibitors and lead to fever and seizures. This effect can last for up to two weeks after discontinuation of Elavil. MAO inhibitors are potentiated by decongestants, so the decongestant should be withheld while the patient is taking the MAO inhibitor or else the MAO inhibitor dosage should be adjusted accordingly. Patient B) Force fluids and increase the intake of sodium to help rid the patient's body of excess lithium.
What adverse effects are associated with the tricyclic antidepressants?
The anticholinergic effects of tricyclics may cause dry mouth, constipation, urinary retention, and rapid heartbeat. Alpha-blocking actions may cause postural hypotension, blurred vision, and drowsiness. In addition, they may cause CNS stimulation, seizures, and cardiac arrhythmias.
Difference between SSRI and SNRI
The main difference between SSRIs and SNRIs is that SSRIs prevent the reuptake of serotonin and SNRIs prevent the reuptake of serotonin and norepinephrine. Serotonin and norepinephrine are substances that the brain uses to send messages from one nerve cell to another. They are also called neurotransmitters.
How do the selective serotonin reuptake inhibitors (SSRI) produce their antidepressant effect?
The selective serotonin reuptake inhibitors (SSRI) are a group of drugs that have a very selective action to block the reuptake of serotonin (5HT) back into the serotonergic nerve endings. This action increases the concentration of 5HT in the synaptic cleft, which results in increased stimulation of serotonin receptors. The increase in 5HT activity in the limbic and cerebral cortical areas of the brain is believed to contribute to the antidepressant effect.
Explain the mechanism of action of the tricyclic antidepressants.
Tricyclic antidepressants block the reuptake of norepinephrine and serotonin back into the neuronal nerve endings of the brain. As a result there is an accumulation of these neurotransmitters in the synaptic clefts. This action increases the level of neuronal activity of norepinephrine and serotonin and alleviates the symptoms and dysfunction of depression.
Difference between Tricyclic and SSRI
Tricyclic antidepressants usually have more of an effect on norepinephrine levels than on serotonin levels. SSRIs also cause more serotonin to be available for neurons to use, by selectively inhibiting serotonin transporters
psychomotor stimulants
amphetamine or related drug that increases mental and physical activity
Lithium
an element similar to sodium that is used in the treatment of mania and bipolar disorder
exogenous, or reactive, depression
depression caused by external factors or life events, first major type of depression, usually doesn't involve drug treatment
difference between mania and depression
depression is characterized by a depressed mood with feelings of hopelessness. Mania is the opposite characterized by hyperexcitability and elation (great happiness)
major depressive disorder (MDD)
depression that arises from within an individual and requires psychotherapy and drug treatment, second major type of depression
monoamine oxidase (MAO)
enzyme that inactivates norepinephrine and serotonin. The normal function of MAO is to break down norepinephrine and serotonin into metabolites that are excreted by the kidneys. MAO prevents the build up of excessive levels of norepinephrine and serotonin in the brain and other body tissue.
Drug interactions of Tricyclic Antidepressants and Anticonvulsants
increased possibility of seizures
Drug interactions of Tricyclic Antidepressants and alcohol
increased sedation
depression
mental state characterized by depressed mood, with feelings of frustration and hopelessness
mania
mental state of excitement, hyperactivity and excessive elevation of mood
MAOIs
monoamine oxidase inhibitors, antidepressant drugs that inhibit the enzyme, MAO so that the norepinephrine and serotonin can stay in the synaptic celft
bipolar mood disorder
mood disorder where episodes of mania and depression occur alternately