Alternative applications of “antidepressants”
Although the evidence of efficacy of antidepressants, as a class, is not as convincing as for other types of drugs, there is growing clinical and research evidence to support a widening range of potential indications of these drugs. The partial success of the SSRIs as a group in ameliorating
OCD is encouraging, as is the utility of TCAs (especially imipramine) and MAO inhibitors (less so fluoxetine, not bupropion) in blocking the episodic, acute autonomic expression of panic. The range of disorders suspected of being related to OCD and in which serotonin-enhancing treatments are being explored, includes eating disorders, hair-pulling (trichotillomania) and other repetitive habits, compulsive gambling, kleptomania, premenstrual dysphoria, and perhaps body dysmorphic disorder. Antidepressants have a scientifically demonstrated but incompletely defined place in the overall management of patients with bulimia nervosa and may have an adjunctive role in anorexia nervosa. Some chronic pain syndromes (particularly with tertiary-amine TCAs in moderate doses), chronic fatigue, and sleep apnea may be helped with an antidepressant, and narcolepsy may be benefited by certain antidepressants (clomipramine) as well as stimulants. Attention deficit-hyperactivity disorder (ADHD) also responds to antidepressants (desipramine or imipramine, probably nortriptyline, possibly bupropion), whereas the record of effectiveness of antidepressants in pediatric depression is less convincing, and for unclear reasons that do not include doses, blood levels, or strong placebo response. Antidepressants (nortriptyline, desipramine) as well as stimulants (methylphenidate) may be useful in mild dementia-depression syndromes of the elderly, but benefits of the safer SSRIs in the elderly is less clear.
Adverse effects of antidepressants
Characteristic side effects of antidepressant drugs, as a group, include annoying and sometimes dangerous autonomic effects. Some of these (especially xerostomia, defective visual accommodation, acute glaucoma, mild tachycardia, constipation, urinary retention, and confusion) have been ascribed to the appreciable antimuscarinic actions of most TCAs, especially the tertiaryamine subgroup, which also carry elevated risks of sedation and postural hypotension. On the other hand, sexual dysfunction (especially ejaculatory incompetence) is routine with most SSRIs and can also occur occasionally with TCAs and with agents virtually without anticholinergic-parasympathetic activity (MAO inhibitors, and especially phenelzine in commonly used doses >45 mg/day), possibly due to a shift toward adrenergic-sympathetic dominance; priapism associated with trazodone may be due to antiadrenergic actions. TCAs and MAO inhibitors are associated with weight gain, which can become a significant medical problem and often leads to discontinuation of treatment; some relatively stimulating antidepressants (bupropion, fluoxetine) have a low risk of weight gain but may tend to induce agitation and insomnia. Risk of life-threatening cardiac arrhythmias with clinical doses of antidepressants is greatly exaggerated, although these can occur in acute overdoses on the order of one or two weeks supply; the quinidine-like actions of most TCAs contraindicate their use with other cardiac depressants. Sustained, usually mild, elevation of diastolic blood pressure has been found with TCAs and MAO inhibitors. Some of the newer antidepressants (bupropion, SSRIs, nefazodone) are much less likely than TCAs to induce life-threatening toxic cardiovascular effects or delirium on acute overdoses; indeed, the SSRIs have largely displaced the TCAs for use in cardiac patients. Nevertheless, most SSRIs (less with sertraline and venlafaxine) inhibit hepatic microsomal cytochrome-P450 oxidases, to interact with and increase circulating concentrations of many other drugs, with an increased risk of toxic effects. Bupropion, clomipramine and maprotiline carry a dose-dependent risk of inducing epileptic seizures.