APA Annual Meeting Highlights New Research

(The following are highlights of new research presented at the 2000 American Psychiatric Association Annual Meeting. Additional highlights can be found in "APA Meeting Highlights New Research," in the February issue of Psychiatric Times, p23-Ed.)

This study was conducted to evaluate the efficacy of bupropion (Wellbutrin) sustained release (SR) in treating dysthymic disorder. Subjects meeting DSM-IV criteria for dysthymic disorder were enrolled in this eight-week, open-label study. Bupropion SR was initiated with 150 qd and increased to a maximum of 200 mg bid for 21 patients.

Of the 21 subjects, 15 were treatment responders, with response defined as 50% drop in Hamilton Rating Scale for Depression (HAM-D) score. Patients with a diagnosis of past alcohol(Drug information on alcohol) or chemical abuse were significantly less likely to respond to bupropion SR. Minor side effects were reported. Neither sexual dysfunction nor weight gain was reported. The findings suggested that bupropion SR was not only effective in treating dysthymic disorder but also highly tolerable among patients (Hellerstein DJ et al., NR702).

Antidepressant-induced sexual dysfunction (AISD) has become an important clinical side effect since the advent of selective serotonin reuptake inhibitors and the newer generation of antidepressants. Each of the major classes of antidepressants is associated with variable rates of sexual dysfunction. The early data in package inserts regarding AISD's prevalence are grossly underestimated because studies used-by default-a "don't ask, don't tell" methodology. In head-to-head studies using established rating scales to measure sexual functioning before and after treatment, findings indicated that bupropion, nefazodone(Drug information on nefazodone) (Serzone) and mirtazapine(Drug information on mirtazapine) (Remeron) are associated with the least incidence of AISD. On the other hand, fluoxetine(Drug information on fluoxetine) (Prozac), sertraline(Drug information on sertraline) (Zoloft), paroxetine(Drug information on paroxetine) (Paxil), citalopram(Drug information on citalopram) (Celexa) (the SSRIs) and venlafaxine (Effexor) are associated with substantial rates of AISD. Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have a long history of AISD as well, but the rates are less clear because of methodological limitations (Nierenburg AA, Symposium 2B).

Researchers have reported that smokers with a history of depression who succeed in smoking cessation are at risk for new episodes of depression. As one might assume, this has serious ramifications for patients who smoke. New episodes occur not only in the immediate withdrawal period but also for months after cessation.

Antidepressants, bupropion in particular, have effectively aided smoking cessation, whether or not the patient is depressed. There is also evidence that the TCA nortriptyline(Drug information on nortriptyline) (Pamelor) may be useful. No study has shown SSRIs to be beneficial (Glassman AH, Symposium 6B).

Short-term effects of antidepressant drugs on body weight may be different from those seen during chronic therapy. Early in treatment, SSRIs typically produce weight loss, but during ongoing therapy some patients gain substantial weight. This is a common occurrence according to anecdotal and non-placebo-controlled studies. Mirtazapine causes significant weight gain early in treatment, but patients lose the added weight over time. Nefazodone appears to be weight neutral, and bupropion can actually cause weight loss (Sussman N, Symposium 14B).

Both depression and pharmacologic treatment of depression are associated with sexual dysfunction. Most patients (70% to 80%) with major depressive disorder (MDD) experience decreased libido. To improve their quality of life, several strategies are available to manage the medication-induced sexual dysfunction. One such strategy is switching to an antidepressant with minimal effects on sexual functioning, such as bupropion, mirtazapine or nefazodone. In fact, substituting an SSRI with bupropion SR is an effective alternative in at least 55% of patients. Other strategies include waiting for spontaneous remission, decreasing the antidepressant dose, prescribing drug holidays and adding a pharmacologic antidote for sexual dysfunction (Clayton ALH et al., Symposium 14A).

While there are currently no reliable methods for determining which antidepressant is most likely to benefit an individual depressed patient, there are some inferences that offer helpful guidelines: 1) serotonergics may be more beneficial in anxious, angry, irritable and impulsive (demodulated) states; 2) catecholaminergics may be more effective in apathetic and fatigued (deactivated) states; and 3) dual-mechanism medications may be more efficacious in melancholic and other mixed states.

To test such targeted treatment and improve results in practice, for the past decade, private outpatients suffering from MDD have been managed by giving SSRIs to patients in demodulated states, catecholaminergics (such as bupropion) to those in deactivated states, and venlafaxine or dual-mechanism combinations (such as fluoxetine and bupropion) to patients in mixed states. In comparing the randomly selected charts of 100 recent targeted-treatment cases with those of a similar group in the 1980s whose treatment was not targeted in this way, researchers found that 95% of patients globally improved in the targeted group compared to 65% in the non-targeted group (Metzner RJ, Symposium 35D).