Discontinuation of antidepressants
The optimal duration of antidepressant therapy for patients treated for depressive symptoms (without a depressive disorder) is unknown. Patients with a depressive disorder who achieve a beneficial response to antidepressant pharmacotherapy should continue treatment for a minimum of 4 to 6 months after depression resolves. When patients are discontinuing antidepressant medications, TCA doses should be tapered by approximately 25% per week to avoid cholinergic rebound (e.g., hypersalivation, diarrhea). In patients who experience intolerable adverse effects, however, doses may be tapered quickly. With the exception of fluoxetine, gradual tapering is advised when decreasing doses or discontinuing treatment for all SSRIs. Other antidepressants with short half-lives, such as venlafaxine, also should be tapered gradually. Withdrawal symptoms, both somatic and psychological, frequently emerge after abrupt discontinuation, during intermittent noncompliance, and sometimes during dose reduction; though these symptoms are generally mild, short-lived, and self-limiting, they can be distressing and may lead to missed workdays and decreased productivity. Mild symptoms can often be treated by reassuring a patient that they are usually transient. For more severe symptoms, it may be necessary to reinstate the dosage of the original antidepressant and slow the rate of taper. Symptoms of discontinuation may be mistaken for physical illness or relapse into depression and misdiagnosis may lead to unnecessary, costly tests and treatment. Thus, health care professionals need to be educated about the potential adverse effects of SSRI discontinuation.
TCAs can produce abnormal myocardial conduction; thus, a cardiac history and a recent EKG should be obtained in patients with a history of cardiac problems. Many tricyclic antidepressants have a sedating effect; therefore, treatment typically is started at low doses at bedtime. The main exception is desipramine, which some patients find mildly stimulating and can be administered in the morning to reduce insomnia, if it develops. Daily doses are increased slowly every few days or at weekly intervals until symptoms improve. Many patients become tolerant to the drugs' sedative effects, and total daily doses may be divided and given during patients' waking cycles.
TCAs are still regarded as first-line agents for severe, major depression; however, SSRI use is increasing for that indication because of the effectiveness of SSRIs and the low risk of clinically significant side effects that are associated with TCAs, such as cardiac arrhythmias, hypotension, and anticholinergic effects. In addition, TCAs are highly toxic on overdose. Side effects commonly associated with the SSRIs include nausea, vomiting, diarrhea, somnolence, insomnia, headache, confusion, dizziness, asthenia, and sexual dysfunction. Drug-specific adverse effects associated with fluoxetine include gastric distress, brief periods of anxiety or agitation, and anorgasmia in females. Treatment with sertraline is sometimes complicated by dyspepsia, tremor, and ejaculatory delay in men.
The pharmacokinetic profiles of SSRIs permit them to be given once a day, thus improving patient compliance.[Level of evidence: II] Sertraline and paroxetine have a half-life of approximately 20 hours; thus, steady-state systemic concentrations can be achieved within 1 week after starting treatment and altering dosage or administration schedules. In comparison, repeated dosing appears to inhibit fluoxetine metabolism; consequently, both fluoxetine and its active metabolite, norfluoxetine, may be present in the body for weeks after discontinuing treatment.