A randomized, single-blind, comparison of venlafaxine with paroxetine in elderly patients suffering from resistant depression

Abstract

It is estimated that up to 45% of patients with depression do not have an adequate response to a first trial of antidepressant therapy with even higher reported rates for the elderly patients. To compare the efficacy and the tolerability of venlafaxine vs. paroxetine in elderly patients suffering from resistant major depression, who did not respond to at least two previous adequate trials of antidepressants. Patients entered an 8-week single-blind study. Patients were rated using the Clinical Global Impression Scale, Hamilton Rating Scale for Depression, and the Geriatric Depression Scale. Assessments were performed at baseline and on days 7, 14, 21, 28, 42 and 56. Side effects were recorded in a systemic manner. Thirty patients were included in the study, (17 women, 13 men; mean age=75.9 years, range: 68-83) and all had completed the 6-week trial. Mean dose of venlafaxine used was 165 mg/day (SD=73.8; range 75-300 mg). Mean dose of paroxetine used was 26 mg/day (SD=15.04; range 10-60 mg). Nine patients treated with venlafaxine (60%) and five patients treated with paroxetine (33%) remitted after 8 weeks of treatment. Four patients treated with venlafaxine and eight patients treated with paroxetine failed to respond. Significant improvement in Hamilton Rating Scale for Depression scores between baseline and endpoint were observed in both groups of patients. The mean Hamilton Rating Scale for Depression change for paroxetine was -12.5 and for venlafaxine -19.1 (P<0.05). The mean Geriatric Depression Scale change for paroxetine was -3.2 and for venlafaxine -6.0 (P<0.3). The mean Clinical Global Impression Scale change was -2.3 for paroxetine and -3.5 for venlafaxine (P<0.05). Venlafaxine was significantly superior to paroxetine on Clinical Global Impression Scale and Hamilton Rating Scale for Depression measures. Side effects were transient and did not differ between treatment groups. Elderly depressed patients resistant to previous treatments had responded to a trial of paroxetine or venlafaxine. Remission rates were higher for venlafaxine and tolerability was acceptable for both compounds.

A Systematic Review of Treatments for Refractory Depression in Older People

“…In the trial comparing selegiline to placebo, responders were older on average than nonresponders (25). The studies variously defined resistant depression as failure to respond to at least one antidepressant (16,(19)(20)(21)(22)26), an antidepressant and a psychological therapy (14), an antidepressant with augmentation (17), or at least two antidepressants (13,(23)(24)(25). Many of the participants had also failed to respond to ECT, but none of the studies specified ECT treatment response in its inclusion criteria.…”

“…One of these was not blinded (20), one was a single-blind study (23), and one was a double-blind study (25). One was placebo controlled, and the other two compared two active treatments (20,23).…”

“…Among those studies that included people with psychotic depression, two included antipsychotic medication in the trial treatment regimen (13,18), three were naturalistic studies of lithium augmentation in which participants did not receive antipsychotics during the study period (16,22,26), two permitted haloperidol and risperidone to be prescribed as judged necessary by clinicians (20, 21) (in one, 17/29 patients received antipsychotics [20], while the other did not specify), one explicitly excluded antipsychotics (25), and one did not specify a policy regarding use of antipsychotics and did not report that they were used (23). Table 1 and Figure 2 give details of the included studies.…”

“…No serious side effects were reported, and no side effects were more common with selegiline compared with placebo. Dosing for the eight responders was switched to Paroxetine [23] Selegiline [25] Tricyclic or venlafaxine + lithium [20] Phenelzine [20] Sequential treatment program [21] Tricyclic + lithium [16] Risperidone + citalopram [13] Paroxetine + lithium, bupropion, or nortriptyline [14] Antidepressant + lithium [22] Duloxetine [19] Aripiprazole augmentation [24] Phenelzine [17] Venlafaxine [15] Tricyclic + lithium [18] Tricyclic + lithium [26] a clinically available MAOI, and informal follow-up for 6 months revealed no substantial relapses. Although one of the products of selegiline metabolism is amphetamine, significant decreases in activation, mania, anxiety, and self-rated irritability with selegiline suggested that amphetamine-like effects did not occur.…”

“…Our definition of treatmentrefractory depression was very inclusive, and many authorities would cite failure to respond to adequate trials of at least two antidepressants as a necessary criterion in any definition of treatment resistance. We therefore judged the two randomized controlled trials that used this definition as the most valid studies (23,25).…”