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1. Which of the following drugs is indicated for obsessive-compulsive disorder?
The correct answer is paroxetine.
Paroxetine is an oral antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, a group that includes fluoxetine and sertraline. Paroxetine is structurally distinct from tricyclic antidepressants and monoamine oxidase inhibitors. Paroxetine has no active metabolites and has the highest specificity for serotonin of all the SSRIs. It is efficacious in depression resistant to other antidepressants and in depression complicated by anxiety. Paroxetine was originally approved by the FDA in December 1992 for the treatment of major depression and subsequently approved for the treatment of obsessive-compulsive disorder (OCD). It was approved for the treatment of panic disorder in May 1996.
2. Which of the following has a clinically significant drug interaction with nortriptyline?
The correct answer is epinephrine.
Nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline. Nortriptyline is similar to protriptyline. Nortriptyline is used to treat depression and for the management of chronic, severe neurogenic pain. Some efficacy has been reported with nortriptyline in phobic disorder† and panic disorder†. Nortriptyline was approved as an antidepressant by the FDA in 1964.
Tricyclic antidepressants (with the exception of doxepin in doses <150 mg/day) block the uptake of guanadrel, guanethidine, and methyldopa into norepinephrine neurons, preventing the expected antihypertensive effects. Reserpine and other rauwolfia alkaloids can have decreased antihypertensive effects in the presence of tricyclic antidepressants.
3. Which of the following is a contraindication to trazodone?
The correct answer is bipolar disorder.
Trazodone is an oral antidepressant, unrelated to other known antidepressants. It possesses some similarities of action to other antidepressant drugs, however, and also has some action as an anxiolytic. Trazodone is used in the treatment of major depression, generalized anxiety disorder†, and insomnia†. Trazodone was approved by the FDA in 1981.
All effective antidepressants can transform depression into mania in predisposed individuals (e.g., bipolar disorder). The usual presentation of this switch is the sudden appearance of insomnia. The antidepressant should be held and appropriate therapy to treat the manic symptoms initiated. Therapeutic doses of lithium (and possibly carbamazepine or valproate) are effective in suppressing the switch process.
4. Of the following, which is most likely to cause abdominal pain as an adverse reaction?
The correct answer is fluvoxamine.
Fluvoxamine is an oral antidepressant drug of the selective serotonin reuptake inhibitors (SSRIs) class. The SSRIs are structurally distinct from the tricyclic antidepressants and monoamine oxidase inhibitors. The most important clinical distinction of the SSRIs is their extremely high specificity for blocking the reuptake of serotonin compared to their effects on other known neurotransmitters such as norepinephrine, acetylcholine, histamine, or dopamine. Fluvoxamine has the shortest half-life of all the SSRIs. Sedation is more common with fluvoxamine than with other SSRIs (e.g., fluoxetine, sertraline). Anorexia and weight loss is less of a concern with fluvoxamine than with fluoxetine. Fluvoxamine is currently approved for use in obsessive-compulsive disorder (OCD) but has also has been used in the treatment of major depression†, ethanol withdrawal†, post traumatic stress disorder†, obesity†, bulimia nervosa†, schizophrenia†, and panic disorder†. Fluvoxamine was approved by the FDA for treatment of obsessive-compulsive disorder on December 5, 1994. Approval for use of fluvoxamine in treatment of major depression is not expected until late 1995 or early 1996. Under the General Agreement on Tariffs and Trade (GATT), the patent expired March 19, 1996.
Gastrointestinal complaints are the most commonly seen side effect with fluvoxamine. Nausea/vomiting are the most common side effects occurring in approximately 16% of patients. Diarrhea, constipation, dyspepsia, abdominal pain, xerostomia, and anorexia are experienced in less than 4% of patients. Nausea usually subsides after a few weeks of therapy but occasionally is severe enough to necessitate discontinuation of the drug. Nausea occurs more frequently with fluvoxamine than with tricyclic antidepressant drugs. Anorexia and weight loss is not a major side effect or concern of fluvoxamine, in contrast with fluoxetine-treated patients. There have been reports of fluvoxamine-induced elevated hepatic enzymes.
5. Of the following, which is most likely to cause dizziness as an adverse reaction?
The correct answer is sertraline.
Sertraline is an oral antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type. It is similar to fluoxetine and paroxetine. Like these drugs, sertraline is structurally distinct from tricyclic antidepressants and monoamine oxidase inhibitors. Sertraline has one active metabolite and the lowest potential for drug interactions involving CYP2D6 (cytochrome P-450 isoenzyme 2D6) of the SSRIs. Sertraline has also been used in the treatment of obsessive-compulsive disorder (OCD). Sertraline was approved by the FDA in December 1991 for the treatment of major depression. As of May 1995, sertraline is undergoing FDA review for treatment of OCD.
Insomnia is the most commonly observed CNS adverse effect, occurring in ~16% of patients treated with sertraline; although this is a common symptoms associated with depression. Somnolence, drowsiness, dizziness, tremor, fatigue, and agitation were observed in 6—13% of patients treated with sertraline. Headache was observed in ~20% of patients treated with sertraline, although this rate was almost equal to the placebo group. Approximately 4% of patients report blurred vision.
6. For which of the following conditions is bupropion indicated?
The correct answer is major depression.
Bupropion is an oral antidepressant drug of the aminoketone class. It is not a tricyclic antidepressant and is unrelated to other known antidepressants. Bupropion has been well tolerated in patients experiencing orthostatic hypotension with tricyclic antidepressant drugs, however, it shows a greater potential for causing seizures than other antidepressants. Bupropion is used to treat major depression. It was originally approved by the FDA in December 1985 but subsequently removed from marketing due to concern over drug-induced seizures. It was reintroduced in July 1989. Bupropion is currently undergoing investigation for use in combination with nicotine patches for treating the symptoms of smoking cessation. A twice-daily dosage formulation is also currently under investigation.
Dosing information for bupropion in major depression can be found on the Dosage screen.
7. Which of the following is contraindicated in elderly?
The correct answer is nefazodone.
Nefazodone is a new oral antidepressant with a mechanism of action distinct from other antidepressants. Nefazodone is structurally similar to trazodone but nefazodone causes less sedation or orthostatic hypotension. Nefazodone is as effective as other antidepressants in treating major depression but lacks cardiovascular toxicity seen with tricyclics and does not cause restlessness or insomnia frequently associated with the selective serotonin reuptake inhibitors and does not inhibit REM sleep. Nefazodone was FDA approved in December 1994 for treatment of major depression.
Use of nefazodone in elderly patients has shown that there is an increase in AUC and Cmax in these patients (see Pharmacokinetics). However, with multiple dosing, this difference is much smaller. It is recommended that these patients be started at one-half the initial dose and titrated as normally indicated.
8. Which of the following has a clinically significant drug interaction with maprotiline?
The correct answer is metoclopramide.
Maprotiline is an oral tetracyclic antidepressant drug of dibenzo-bicyclo-octadiene derivation. It is used for various types of depressive disorder such as unipolar depression, depressive neurosis, and the depressive phase of bipolar disorder. Most references consider maprotiline similar to traditional tricyclic antidepressants. Maprotiline is also effective in treating anxiety associated with depression. Maprotiline was approved for use by the FDA in 1980.
Tricyclic antidepressants used concomitantly with strong anticholinergic agents, such as anticholinergics; HÀ-blockers; cyclobenzaprine; antipsychotics (haloperidol, loxapine, molindone, phenothiazines, or thioxanthenes); amoxapine; or metoclopramide, will increase the anticholinergic and sedative effects. Concomitant therapy should be avoided whenever possible. If necessary, doses of both drugs should be started lower and increased cautiously with careful monitoring.
9. For which of the following conditions is desipramine indicated?
The correct answer is major depression.
Desipramine is a tricyclic antidepressant of the dibenzazepine type, but it also is the active metabolite of imipramine. Desipramine is used in the management of eating disorders, especially bulimia. It is also used in treating symptoms of diabetic neuropathy and as an adjunct to treatment for cessation of cocaine dependence. Desipramine was approved by the FDA in 1964.
10. Which of the following is a contraindication to nortriptyline?
The correct answer is children.
Nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline. Nortriptyline is similar to protriptyline. Nortriptyline is used to treat depression and for the management of chronic, severe neurogenic pain. Some efficacy has been reported with nortriptyline in phobic disorder† and panic disorder†. Nortriptyline was approved as an antidepressant by the FDA in 1964.
Tricyclic antidepressants should be used with caution in patients (especially children and elderly) with cardiac disease because of the alterations in ECG patterns. Many adverse cardiovascular effects are associated with the use of tricyclic antidepressant drugs, which could lead to complete cardiac collapse and sudden death. Although these events are more likely to occur after acute overdose, patients with cardiovascular disease should be closely monitored and regular ECG tracings made. Tricyclic antidepressants should not be given to patients who are in the acute recovery phase following myocardial infarction; sudden death is possible.
11. Which of the following drugs has a clinically significant interaction with nifedipine?
The correct answer is nefazodone.
Nefazodone is a new oral antidepressant with a mechanism of action distinct from other antidepressants. Nefazodone is structurally similar to trazodone but nefazodone causes less sedation or orthostatic hypotension. Nefazodone is as effective as other antidepressants in treating major depression but lacks cardiovascular toxicity seen with tricyclics and does not cause restlessness or insomnia frequently associated with the selective serotonin reuptake inhibitors and does not inhibit REM sleep. Nefazodone was FDA approved in December 1994 for treatment of major depression.
Nefazodone should not be administered to patients receiving terfenadine or astemizole because nefazodone inhibits cytochrome, the enzyme which metabolizes all three drugs. Inhibition of this enzyme by nefazodone results in increased plasma concentrations of both terfenadine and astemizole. Increased plasma concentrations of terfenadine or astemizole are associated with QT prolongation and rare cases of serious cardiovascular adverse events, including death due to torsade de pointes. Dosage adjustments are necessary when triazolobenzodiazepines (alprazolam and triazolam) are administered with nefazodone because nefazodone inhibits cytochrome, the enzyme that metabolizes all three drugs. The half-life and AUC for triazolam are increased 4-fold and for alprazolam, they are increased 2-fold. Peak concentrations are increased 1.7 and 2-fold for triazolam and alprazolam, respectively. Neither alprazolam nor triazolam has an effect on nefazodone plasma concentrations. Initial doses of alprazolam and triazolam should be reduced by 50% and 75%, respectively. Diazepam and other benzodiazepines that are metabolized by oxidation should also be used cautiously in patients receiving nefazodone. Although no reports of a clinical interaction have been identified, an interaction with nefazodone may occur with other drugs due to the ability of nefazodone to inhibit the activity of the cytochrome IIIAÃ isoenzyme. Because of this, nefazodone can interfere with the clearance of drugs metabolized via this pathway, resulting in increased plasma concentrations. Examples of drugs metabolized by the CYP3A4 isoenzyme that may be affected by nefazodone include: alprazolam, astemizole, carbamazepine, cisapride, cyclosporine, diazepam, diltiazem, erythromycin, felodipine, lidocaine, lovastatin, midazolam, nifedipine, quinidine, simvastatin, terfenadine, triazolam, and verapamil. Toxicity with any of these agents is possible if nefazodone is added or used concurrently.
12. Which of the following is contraindicated in surgery?
The correct answer is imipramine.
Imipramine is an antidepressant drug of the dibenzazepine type, referred to as a tricyclic because of its chemical structure. Imipramine was first synthesized in the late 1940s. It is used to treat depression and childhood enuresis. Imipramine also has been used in the management of neurogenic pain†, attention-deficit hyperactivity disorder (ADHD)† in children over age 6, eating disorders, and panic or phobic disorder, although these are not FDA-approved uses. Imipramine was approved by the FDA for use for depression in 1959 and for enuresis in 1973. It is considered the prototype tricyclic antidepressant.
Tricyclic antidepressant therapy should be discontinued several days before elective surgery because of the risk of hypertensive episodes.
13. Which of the following has a clinically significant drug interaction with fluvoxamine?
The correct answer is cimetidine.
Fluvoxamine is an oral antidepressant drug of the selective serotonin reuptake inhibitors (SSRIs) class. The SSRIs are structurally distinct from the tricyclic antidepressants and monoamine oxidase inhibitors. The most important clinical distinction of the SSRIs is their extremely high specificity for blocking the reuptake of serotonin compared to their effects on other known neurotransmitters such as norepinephrine, acetylcholine, histamine, or dopamine. Fluvoxamine has the shortest half-life of all the SSRIs. Sedation is more common with fluvoxamine than with other SSRIs (e.g., fluoxetine, sertraline). Anorexia and weight loss is less of a concern with fluvoxamine than with fluoxetine. Fluvoxamine is currently approved for use in obsessive-compulsive disorder (OCD) but has also has been used in the treatment of major depression†, ethanol withdrawal†, post traumatic stress disorder†, obesity†, bulimia nervosa†, schizophrenia†, and panic disorder†. Fluvoxamine was approved by the FDA for treatment of obsessive-compulsive disorder on December 5, 1994. Approval for use of fluvoxamine in treatment of major depression is not expected until late 1995 or early 1996. Under the General Agreement on Tariffs and Trade (GATT), the patent expired March 19, 1996.
Although no data are available, it is possible that inhibitors of hepatic enzymes such as cimetidine may affect fluvoxamine pharmacokinetics. A significant interaction has been suggested for cimetidine-paroxetine; fluvoxamine may be similarly affected by cimetidine. Until more data are available, cimetidine should be used cautiously in patients receiving fluvoxamine.
14. Of the following, which is a clinically significant adverse reaction due to venlafaxine therapy?
The correct answer is anxiety.
Venlafaxine is an oral antidepressant agent that is structurally unrelated to other available antidepressants. It is indicated for the treatment of major depression. Venlafaxine appears to be effective in treating patients with melancholia, a severe form of depression. Its side effect profile is similar to that of the selective serotonin reuptake inhibitors (SSRIs). It should not be used in patients who are receiving or have recently received MAOI therapy. Venlafaxine was approved by the FDA in December 1993.
Other adverse events reported by the manufacturer that required discontinuation of venlafaxine treatment and occurred at an incidence of 5% or greater or twice that of placebo are as follows: anxiety (6%); asthenia (12%); blurred vision (6%); constipation (15%); diaphoresis (12%); nausea/vomiting (37%/6%); insomnia (18% vs 10% for placebo); nervousness (13%); xerostomia (22%); and tremor (5%).
15. Which of the following drugs has a clinically significant interaction with furazolidone?
The correct answer is trazodone.
Trazodone is an oral antidepressant, unrelated to other known antidepressants. It possesses some similarities of action to other antidepressant drugs, however, and also has some action as an anxiolytic. Trazodone is used in the treatment of major depression, generalized anxiety disorder†, and insomnia†. Trazodone was approved by the FDA in 1981.
Monoamine oxidase inhibitors (MAOIs), such as furazolidone, isocarboxazid, pargyline, phenelzine, procarbazine, selegiline, or tranylcypromine) used concurrently with trazodone can cause hyperpyrexia, hypertension, or seizures. An interval of 14 days is recommended between cessation of therapy with an irreversible MAOI and the initiation of trazodone therapy.
16. For which of the following conditions is imipramine indicated?
The correct answer is neuropathic pain†.
Imipramine is an antidepressant drug of the dibenzazepine type, referred to as a tricyclic because of its chemical structure. Imipramine was first synthesized in the late 1940s. It is used to treat depression and childhood enuresis. Imipramine also has been used in the management of neurogenic pain†, attention-deficit hyperactivity disorder (ADHD)† in children over age 6, eating disorders, and panic or phobic disorder, although these are not FDA-approved uses. Imipramine was approved by the FDA for use for depression in 1959 and for enuresis in 1973. It is considered the prototype tricyclic antidepressant.
Dosing information for imipramine in neuropathic pain† can be found on the Dosage screen.
17. Which of the following is a contraindication to paroxetine?
The correct answer is suicidal ideation.
Paroxetine is an oral antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, a group that includes fluoxetine and sertraline. Paroxetine is structurally distinct from tricyclic antidepressants and monoamine oxidase inhibitors. Paroxetine has no active metabolites and has the highest specificity for serotonin of all the SSRIs. It is efficacious in depression resistant to other antidepressants and in depression complicated by anxiety. Paroxetine was originally approved by the FDA in December 1992 for the treatment of major depression and subsequently approved for the treatment of obsessive-compulsive disorder (OCD). It was approved for the treatment of panic disorder in May 1996.
All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy. Paroxetine should be prescribed in the smallest quantity appropriate for the patient.
18. Of the following, which is a clinically significant adverse reaction due to trazodone therapy?
The correct answer is tremor.
Trazodone is an oral antidepressant, unrelated to other known antidepressants. It possesses some similarities of action to other antidepressant drugs, however, and also has some action as an anxiolytic. Trazodone is used in the treatment of major depression, generalized anxiety disorder†, and insomnia†. Trazodone was approved by the FDA in 1981.
Muscle tremor and musculoskeletal pain have been reported during therapy with trazodone, which may due to weak skeletal muscle-relaxant activity.
19. Which of the following drugs has a clinically significant interaction with labetalol?
The correct answer is clomipramine.
Clomipramine is similar in structure to the tricyclic antidepressant drugs imipramine and desipramine and is the first drug approved for the treatment of obsessive-compulsive disorder. Anticholinergic and orthostatic hypotensive adverse effects are more pronounced for clomipramine than for the other tricyclic antidepressants. Clomipramine is the most specific of all the tricyclic antidepressants with regard to its ability to inhibit serotonin reuptake versus norepinephrine reuptake. Although clomipramine is used clinically to treat obsessive-compulsive disorder, it is occasionally used for major depression†. It was approved by the FDA for the treatment of OCD in 1991.
Labetalol coadministered with tricyclic antidepressants has been reported to increase the incidence of tremor.
20. Of the following, which is most likely to cause blurred vision as an adverse reaction?
The correct answer is amitriptyline.
Amitriptyline is an oral and parenteral tertiary amine tricyclic antidepressant. It is structurally related to the thioxanthene antipsychotics such as thiothixene. Amitriptyline is also related to the skeletal muscle relaxant cyclobenzaprine, although amitriptyline is not believed to possess muscle-relaxant properties. Amitriptyline is metabolized to nortriptyline, an active metabolite that is also marketed separately. Clinically, amitriptyline is used to treat depression, pain of neuropathic origin, attention-deficit hyperactivity disorder†, functional enuresis† in children, panic disorder†, and phobic disorder†, and to manage some eating disorders†. Amitriptyline was approved by the FDA in 1961.
Ocular manifestations of the anticholinergic actions of tricyclic antidepressants can result in blurred vision due to cycloplegia, mydriasis, and increased intraocular pressure. Increased intraocular pressure can precipitate a crisis in patients with angle-closure glaucoma. Ophthalmological examination is recommended when there are visual changes.
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