Current issues of ACP Journal Club are published in Annals of Internal Medicine


Fluoxetine plus pindolol was more effective than fluoxetine alone in depression

ACP J Club. 1997 Nov-Dec;127:66. doi:10.7326/ACPJC-1997-127-3-066

Source Citation

Pérez V, Gilaberte I, Faries D, Alvarez E, Artigas F. Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment. Lancet. 1997 May 31;349:1594-7.



To determine whether the addition of pindolol to fluoxetine therapy increases the effectiveness and decreases the time to clinical improvement in patients with major depression.


Randomized, double-blind, placebo-controlled trial with 42-day follow-up.


Hospital in Barcelona, Spain.


111 patients (mean age 43 y, 71% women) with unipolar major depression and moderately severe symptoms (a score of ≥ 18 on the 17-item Hamilton depression-rating scale) who were referred from primary psychiatric care centers were included. Exclusion criteria included concomitant psychiatric pathology, suicide risk, organic brain disease or history of seizures, delusions or hallucinations, drug or alcohol abuse in the past 3 months, serious organic illnesses, myocardial infarction in the past 6 months, allergic reactions, concomitant use of other psychotropic drugs, failure to respond to drug treatment in a current depressive episode, and previous treatment failure with fluoxetine.


55 patients were allocated to fluoxetine, 20 mg daily, plus pindolol, 7.5 mg daily. 56 patients were allocated to the same dose of fluoxetine plus placebo.

Main outcome measure

Clinical response defined as a ≥ 50% decrease in the baseline Hamilton depression-rating scale score.

Main results

More patients in the fluoxetine and pindolol group were classified as clinical responders (1-tailed P = 0.04) and achieved a sustained response (1-tailed P = 0.03) compared with those in the fluoxetine and placebo group (Table).


Fluoxetine plus pindolol was more effective than fluoxetine alone in patients with major depression.

Sources of funding: Lilly Spain and Ministry of Health, Spain.

For article reprint: Dr. F. Artigas, Department of Neurochemistry, Consejo Superior de Investigaciones Científicas, Jordi Girona 18-26, 08034 Barcelona, Spain. FAX 343-204-5904.

Table. Fluoxetine and pindolol vs fluoxetine and placebo*

Outcomes at 42 d Fluoxetine and pinodolol EER Fluoxetine and placebo CER RBI (95% CI) ABI |EER-CER| (CI) NNT (CI)
Clinical response 75% 59% 27% (-3% to 68%) 16% (-2% to 32%) NS
Sustained response 69% 48% 43% (4% to 10%) 21% (3% to 38%) 5 (3 to 39)

*NS = not significant. Other abbreviations defined in Glossary; RBI, ABI, NNT, and CI calculated from data in article.


Major depression is common and associated with substantial morbidity and mortality (1). Antidepressant therapy is indicated for moderate and severe depression. Unfortunately, only 60% to 70% of patients respond to antidepressant therapy and the rate of complete remission may be lower. Further, a delay in the onset of action of 4 to 6 weeks often occurs (2). Any pharmacologic intervention that increases the rate of response and decreases the time to clinical improvement would be of major clinical importance.

The study by Pérez and colleagues compared the selective serotonin reuptake inhibitor (SSRI) fluoxetine with the combination of fluoxetine and pindolol. Fluoxetine is a widely prescribed antidepressant that is as effective as tricyclic antidepressants but is safer if taken in overdose and may have a modest advantage in terms of tolerability (3). It is important to note that the SSRIs are as much as 30 times more expensive than the tricyclic antidepressants, and vigorous debate exists about their use as first-line antidepressants.

Although this study confirmed that the combination of fluoxetine and pindolol was more effective than fluoxetine alone, it did not unequivocally confirm that the combination was associated with a decrease in the time to clinical improvement. The improvement in efficacy was of sufficient magnitude to suggest that this combination of medications might have a place in clinical practice. However, before this pharmacologic strategy is adopted in routine clinical practice, further comparative studies are required to confirm the findings. Larger cohort studies are needed to explore the rate of uncommon and rare side effects, consequences of overdose with both agents will need to be explored, and economic evaluations are required to determine the marginal benefit of the combination of pindolol and an SSRI compared with an SSRI alone or a tricyclic alone.

Mark A. Oakley Browne, MB, ChB, PhD
University of AucklandAuckland, New Zealand


1. Klerman GL, Weisman MM. Arch Gen Psychiatry. 1992;49:831-4.

2. American Psychiatric Association practice guidelines for major depressive disorder in adults. Am J Psychiatry. 1990;19(Suppl):87-98.

3. Anderson IM, Tomenson BM. BMJ. 1995;310:2433-8.