Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 12e

Chapter 30: Antidepressants

A 36-year-old woman presents with symptoms of major depression that are unrelated to a general medical condition, bereavement, or substance abuse. She is not currently taking any prescription or over-the-counter medications. Drug treatment is to be initiated with sertraline. In your information to the patient, you would tell her that

(A) Sertraline may take 2 weeks or more to become effective

(B) It is preferable that she take the drug in the morning

(C) Muscle cramps and twitches can occur

(D) She should notify you if she anticipates using other prescription drugs

(E) All of the above

All the statements are appropriate regarding the initiation of treatment with sertraline or any other SSRI in a depressed patient. The SSRIs have CNS-stimulating effects and may cause agitation, anxiety, “the jitters,” and insomnia, especially early in treatment. Consequently, the evening is not the best time to take SSRI drugs. The answer is E.

Concerning the proposed mechanisms of action of antidepressant drugs, which statement is most accurate?

(A) Bupropion inhibits NE reuptake into nerve endings in the CNS

(B) Chronic treatment with tricyclic antidepressants leads to downregulation of adrenoceptors in the CNS

(C) Decreased levels of NE and 5-HT in cerebrospinal fluid is a characteristic of depressed patients before drug therapy

(D) Nefazodone activates 5-HT receptors in the CNS

(E) Selegiline selectively decreases the metabolism of serotonin

The mechanism of action of bupropion is unknown, but the drug does not inhibit either NE or 5-HT transporters. Levels of NE and 5-HT metabolites in the cerebrospinal fluid of depressed patients before drug treatment are not higher than normal. Selegiline is a selective inhibitor of MAO-B, the enzyme form that metabolizes dopamine (see Chapter 28). Nefazodone is a highly selective antagonist at the 5-HT₂ receptor subtype. Downregulation of adrenoceptors appears to be a common feature of chronic treatment of depression with tricyclic drugs such as amitriptyline. The answer is B.

A 34-year-old man who was prescribed citalopram for depression has decided he wants to stop taking the drug. When questioned, he said that it was affecting his sexual performance. You ascertain that he is also trying to overcome his dependency on tobacco products. If you decide to reinstitute drug therapy in this patient, the best choice would be

(A) Amitriptyline

(B) Bupropion

(C) Fluoxetine

(D) Imipramine

(E) Venlafaxine

The SSRIs (eg, fluoxetine) and venlafaxine (an SNRI) can cause sexual dysfunction with decreased libido, erectile dysfunction, and anorgasmia. TCAs may also decrease libido or prevent ejaculation. Bupropion is the least likely antidepressant to affect sexual performance. The drug is also purportedly useful in withdrawal from nicotine dependence, which could be helpful in this patient. The answer is B.

Regarding the clinical use of antidepressant drugs, which statement is most accurate?

(A) Chronic use of serotonin-norepinephrine reuptake inhibitors (SNRIs) increases the activity of hepatic drug-metabolizing enzymes

(B) In the treatment of major depressive disorders, citalopram is usually more effective than paroxetine

(C) Tricyclics are highly effective in depressions with attendant anxiety, phobic features, and hypochondriasis

(D) Weight gain often occurs during the first few months in patients taking SSRIs

(E) When selecting an appropriate drug for treatment of depression, the history of patient response to specific drugs is a valuable guide

No antidepressant has been shown to increase hepatic drug metabolism. MAO inhibitors (not TCAs), though now used infrequently, are the drugs most likely to be effective in depression with attendant anxiety, phobic features, and hypochondriasis. SSRIs are usually associated with weight loss, at least during the first 6 months of treatment. There is no evidence that any SSRI is more effective than another, or more effective overall than a tricyclic drug, in treatment of major depressive disorder. The answer is E.

A patient under treatment for a major depressive disorder is brought to the emergency department after ingesting 30 times the normal daily therapeutic dose of imipramine. Which of the following would be least useful?

(A) Administer bicarbonate and potassium chloride (to correct acidosis and hypokalemia)

(B) Administer lidocaine (to control cardiac arrhythmias)

(C) Initiate hemodialysis (to hasten drug elimination)

(D) Maintain heart rhythm by electrical pacing

(E) Use intravenous diazepam to control seizures

Overdose with imipramine or any other tricyclic antidepressant drug is a medical emergency. The “3 Cs”—coma, convulsions, and cardiac problems—are the most common causes of death. Widening of the QRS complex on the ECG is a major diagnostic feature of cardiac toxicity. Arrhythmias resulting from cardiac toxicity require the use of drugs with the least effect on cardiac conductivity (eg, lidocaine). Hemodialysis does not increase the rate of elimination of tricyclic antidepressants in overdose. The answer is C.

Which drug is an antagonist at 5-HT₂ receptors and widely used for the management of insomnia in depressed patients?

(A) Estazolam

(B) Flurazepam

(C) Trazodone

(D) Triazolam

(E) Zolpidem

All of the drugs listed are effective hypnotic drugs, but only trazodone is an antagonist at 5-HT₂ receptors. Trazodone has wide use as a sleeping aid, especially in patients with symptoms of affective disorder. The answer is C.

A recently widowed 76-year-old woman was treated with a benzodiazepine for several weeks after the death of her husband, but she did not like the daytime sedation it caused even at low dosage. Living independently, she has no major medical problems but appears rather infirm for her age and has poor eyesight. Because her depressive symptoms are not abating, you decide on a trial of an antidepressant medication. Which of the following drugs would be the most appropriate choice for this patient?

(A) Amitriptyline

(B) Citalopram

(C) Mirtazapine

(D) Phenelzine

(E) Trazodone

Older patients are more likely to be sensitive to antidepressant drugs that cause sedation, atropine-like adverse effects, or postural hypotension. Tricyclics and MAO inhibitors cause many autonomic side effects; mirtazapine and trazodone are highly sedating. Citalopram (or another SSRI) is often the best choice in such patients. The answer is B.

SSRIs are much less effective than tricyclic antidepressants in the management of

(A) Bulimia

(B) Chronic neuropathic pain

(C) Generalized anxiety disorder

(D) Obsessive-compulsive disorder

(E) Premenstrual dysphoric disorder

The SSRIs are not effective in chronic pain of neuropathic origin. All the other uses of SSRIs are approved indications with clinical effectiveness equivalent or superior to that of tricyclic drugs. In addition to treatment of chronic pain states and depression the tricyclics are also used to treat enuresis and attention deficit hyperactivity disorder. The answer is B.

Which of the following drugs is most likely to be of value in obsessive-compulsive disorders?

(A) Amitriptyline

(B) Bupropion

(C) Clomipramine

(D) Trazodone

(E) Venlafaxine

Clomipramine, a tricyclic agent, is a more selective inhibitor of 5-HT reuptake than other drugs in the tricyclic group. This activity appears to be important in the treatment of obsessive-compulsive disorder. However, the SSRIs have now become the drugs of choice for this disorder because they are safer in overdose than tricyclics. The answer is C.

To be effective in breast cancer, tamoxifen must be converted to an active form by CYP2D6. Cases of inadequate treatment of breast cancer have occurred when tamoxifen was administered to patients who were being treated with

(A) Amitriptyline

(B) Bupropion

(C) Fluoxetine

(D) Mirtazapine

(E) Phenelzine

Fluoxetine is an inhibitor of hepatic cytochrome P450s, especially CYP2D6, and to a lesser extent CYP3A4. Dosages of several drugs may need to be reduced if given concomitantly with fluoxetine. In the case of tamoxifen, however, its antineoplastic action is dependent on its conversion to an active metabolite by CYP2D6. The answer is C.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.

Chapter 30: Antidepressants

Send Email

Citation

Jump to a Section

Chapter 30: Antidepressants

Pop-up div Successfully Displayed