Digging a bit further down the rabbit hole, the trend of what I'm seeing is that there's no concrete data on pindolol; it may accelerate antidepressant response but does not augment the total antidepressant response over time. In other words, it is ineffective in TRD but may hasten time to therapeutic response in those would have eventually responded to a serotonergic antidepressant without adjunctive pindolol.
Buspar, on the other hand actually
augments serotonergic antidepressants (possibly in part due to a major metabolite's alpha-2 antagonism and/or effects at D2?) and may or may not hasten time to response?
So buspar augmentation is effective in TRD but pindolol is not. Everything else is fuzzy.
What is myth, what is reality, what is the matrix?
Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials.
Authors
Ballesteros J,et al.
Show allBallesteros J, Callado LF.
Journal
J Affect Disord. 2004 Apr;79(1-3):137-47.
Affiliation
Department of Pharmacology, University of the Basque Country, Leioa, Spain.
[email protected]
Comment in
Abstract
BACKGROUND: Contradictory results on the efficacy of pindolol associated with selective serotonin reuptake inhibitors (SSRIs) in depressive illness have been published and no former review has produced an overall figure of its efficacy. This study aims to review the efficacy and tolerability of pindolol plus SSRIs in depressive illness.
METHODS: A meta-analysis of randomised controlled trials (RCTs) comparing pindolol plus SSRIs with placebo plus SSRIs.
RESULTS: Nine RCTs met inclusion criteria. Outcome favoured pindolol at 2 weeks time (N=5; OR=2.8; 95% CI 1.4-5.7), but not at four to 6 weeks (N=7; OR=1.4; 95% CI 0.8-2.7). Results for early outcome studies were robust to sensitivity analysis. Nineteen more studies, averaging null results, would be needed to change the overall probability (P=0.0001) to a non-significant figure.
CONCLUSIONS: Pindolol seems to hasten the response to SSRIs in depression with a timing window circumscribed to the first weeks of treatment.
PMID
15023488 [PubMed - indexed for MEDLINE]
Full text:
Elsevier Science
Does the addition of pindolol accelerate the response to electroconvulsive therapy in patients with major depression? A double-blind, placebo-controlled pilot study.
Authors
Shiah IS,et al.
Show allShiah IS, Yatham LN, Srisurapanont M, Lam RW, Tam EM, Zis AP.
Journal
J Clin Psychopharmacol. 2000 Jun;20(3):373-8.
Affiliation
Department of Psychiatry, The University of British Columbia, Vancouver, Canada.
Abstract
There is evidence that addition of pindolol, a beta-adrenergic/5-hydroxytryptamine-1A antagonist, can accelerate the onset of action of antidepressant medications. The purpose of this study was to determine whether pindolol administration can induce a rapid improvement in depressive symptoms in patients receiving electroconvulsive therapy (ECT) within six ECT treatments. A total of 20 patients with DSM-IV-diagnosed major depression who were undergoing a course of ECT as the clinically indicated treatment were recruited. They were neuroleptic, lithium, and antidepressant free for at least 1 week before the study. Of the 20 patients, 9 patients had been randomly assigned to receive pindolol 2.5 mg three times daily, and 11 patients received identical placebo three times daily for the duration of the first 6 ECT treatments. One of 9 patients in the pindolol group and 4 of 11 patients in the placebo group dropped out of the study. Using an outcome measure of a score < or =12 on the 29-item Hamilton Rating Scale for Depression (HAM-D), the authors found that four (50%) of eight patients responded to the combination treatment of ECT and pindolol within six ECT treatments. In contrast, none (0%) of seven patients who received placebo responded to ECT treatment. Furthermore, both mean 29-item HAM-D and Clinical Global Impression Scale scores after the sixth ECT treatment were significantly lower in patients treated with pindolol compared with those treated with placebo. However, the number of total ECT treatments within a course or the overall efficacy of ECT treatment was not altered by the addition of pindolol. The results of this study suggest that within six ECT treatments, pindolol administration hastens antidepressant effects of ECT in some depressed patients.
PMID
10831027 [PubMed - indexed for MEDLINE]
Effect of pindolol on onset of action of paroxetine in the treatment of major depression: intermediate analysis of a double-blind, placebo-controlled trial. Réseau de Recherche et d'Expérimentation Psychopharmacologique.
Authors
Bordet R,et al.
Show allBordet R, Thomas P, Dupuis B.
Journal
Am J Psychiatry. 1998 Oct;155(10):1346-51.
Affiliation
Réseau de Recherche et d'Expérimentation Psychopharmacologique (REPP), Centre Hospitalier et Universitaire, Lille, France.
[email protected]
Abstract
OBJECTIVE: The purpose of this study was to investigate the effect of pindolol to accelerate the onset of action of paroxetine in patients suffering from major depression.
METHOD: Patients who met DSM-IV criteria for a nonpsychotic disorder, who had no previously treated episode of major depression episode, and who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale were randomly assigned, for the first 21 days, to treatment with paroxetine (20 mg/day) and either pindolol (5 mg t.i.d.) or placebo. Patients were evaluated with the Hamilton depression scale, the Montgomery-Asberg Depression Rating Scale, and Global Clinical Impression (CGI) on days 0 (baseline), 5, 10, 15, 21, 25, 31, 60, 120, and 180.
RESULTS: Intermediate analysis of the first month's results for the first 100 patients (pindolol, N=50; placebo, N=50) was performed. At day 10 there were more improved patients (defined as patients with a maximum score of 10 on the Hamilton depression scale) in the pindolol plus paroxetine group (N=24; 48%) than in the placebo plus paroxetine group (N=13; 26%). At day 5 there was no statistically significant difference, and at day 15 and thereafter, the differences between the two groups disappeared. Hamilton depression scale scores were significantly lower on days 5 and 10 for the pindolol plus paroxetine group (mean=15.7, SD=5.3, and mean=11.7, SD=6.4, respectively) than for the placebo plus paroxetine group (mean=19, SD=5.9, and mean=14.7, SD=6.8); this was also true for Montgomery-Asberg depression scale and CGI scores.
CONCLUSIONS: The addition of pindolol to paroxetine treatment significantly accelerates the onset of therapeutic response in patients suffering from major depression. Nevertheless, the mechanism (pharmacodynamic or pharmacokinetic) of this beneficial effect remains unclear.
PMID
9766765 [PubMed - indexed for MEDLINE]
Free full text:
HighWire Press
Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect? A randomized clinical trial and a meta-analysis of pindolol in nonresistant depression.
Portella MJ,
de Diego-Adeliño J,
Ballesteros J,
Puigdemont D,
Oller S,
Santos B,
Álvarez E,
Artigas F,
Pérez V.
Source
Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Avenue Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain.
[email protected]
Abstract
OBJECTIVE:
Since depression entails not only dramatic personal disruption but also a huge amount of medical and socioeconomic burden, slowness of antidepressant action and difficulties to attain remission are entangled issues to be solved. Given the controversial previous findings with enhancing strategies such as pindolol, we examined whether the speed of selective serotonin reuptake inhibitor (SSRI) action can be truly accelerated with optimized pindolol dosage. Additionally, we aimed at elucidating whether pindolol benefits emerge, particularly in a population with nonresistant depression.
METHOD:
Thirty outpatients with major depressive disorder (DSM-IV criteria) recruited between December 2002 and November 2005 were randomly assigned to receive citalopram + pindolol (5 mg tid) or citalopram + placebo for 6 weeks in a double-blind randomized clinical trial. A meta-analysis of randomized controlled trials of pindolol augmentation in patients with nonresistant depression was also performed. Outcome criteria were based on the 17-item Hamilton Depression Rating Scale. For the meta-analysis, efficacy was assessed by the number of treatment responders at 2 weeks and 4-6 weeks.
RESULTS:
Clinical trial outcomes: Repeated-measures analysis of variance showed a significant group-by-time interaction (P = .01). Cumulative percentage showed a trend for sustained response (odds ratio [OR] = 2.09; 95% CI, 0.914-4.780; P = .08) and a well-defined increased likelihood of sustaining remission (OR = 5.00; 95% CI, 1.191-20.989; P = .03) in pindolol receivers. Median survival time until first response was 65% less in the pindolol group (22 days vs 30 days; P = .03). The negative binomial regression model yielded different rates of response per person-day for pindolol and placebo groups (7.6% vs 4.7%, respectively; P = .03). Meta-analysis: Outcome favored pindolol at 2 weeks' time (relative risk [RR] = 1.68; 95% CI, 1.18-2.39; P = .004) and also at 4-6 weeks' time (RR = 1.11; 95% CI, 1.02-1.20; P = .02).
CONCLUSIONS:
Present findings represent further evidence of the acceleration and enhancement of efficacy with pindolol administered together with SSRIs, displaying a quicker and more pronounced decrease of symptoms in patients with nonresistant major depressive disorder.
TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT00931775.
Once-daily high-dose pindolol for SSRI-refractory depression.
Sokolski KN,
Conney JC,
Brown BJ,
DeMet EM.
Source
VA Long Beach Healthcare System, 5901 East 7th Street (06/116a), Long Beach, CA 90822, USA.
[email protected]
Abstract
Selective serotonin reuptake inhibitor (SSRI) augmentation with the 5-HT1A antagonist pindolol has met with mixed results. Recent studies using positron emission tomography (PET) suggest that pindolol doses used in these studies were too low to effect 5-HT1A autoreceptor blockade. To test the hypothesis that a single higher dose of pindolol would effectively augment antidepressant responses in SSRI-refractory patients, nine subjects with major depression unresponsive to paroxetine 40 mg/day given for 2 months or more were randomized to AM pindolol 7.5 mg (n=4) or placebo (n=5). Subjects were administered the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), the Bech-Rafaelsen Melancholia Scale, and the Zung Depression Inventory at baseline and weeks 1, 2, 3, and 4. Subjects receiving pindolol exhibited significant improvements in all ratings beginning at week 2 which continued through week 4. Aside from transient dizziness and a five-point decrease in systolic/diastolic blood pressure associated with pindolol, no adverse effects were reported. Although results must be verified in a larger sample, these findings support previous studies indicating that pindolol can accelerate antidepressant responses during SSRI therapy. In addition, results reported here suggest that a single high dose of pindolol (7.5 mg) is a more effective augmentation strategy in SSRI-refractory patients compared with the same total dose given at 2.5 mg tid.
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Pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitors: a double-blind, randomized, controlled trial.
Authors
Perry EB,et al.
Show allPerry EB, Berman RM, Sanacora G, Anand A, Lynch-Colonese K, Charney DS.
Journal
J Clin Psychiatry. 2004 Feb;65(2):238-43.
Affiliation
Department of Psychiatry, VA Connecticut Healthcare System, Psychiatry Service-116A, 950 Campbell Avenue, West Haven, CT 06516, USA.
[email protected]
Abstract
BACKGROUND: Studies of pindolol augmentation of antidepressants in major depressive disorder have produced mixed results, and data in treatment-resistant patients are limited. Here, we report on a double-blind, randomized, controlled 6-week study of pindolol augmentation of selective serotonin reuptake inhibitors (SSRIs) in depressed outpatients resistant to SSRI monotherapy.
METHOD: Forty-two outpatients with DSM-IV major depressive disorder who had an insufficient response to an adequate trial of an SSRI (fluoxetine, paroxetine, or sertraline) were randomly assigned to pindolol, 2.5 mg t.i.d., or sham augmentation, in addition to continued SSRI administration. For separate analysis, the control group underwent a single-blinded switch to pindolol, 2.5 mg t.i.d., from week 4 through week 6, while the active group was continued on pindolol augmentation (hemi-crossover design). Change in Hamilton Rating Scale for Depression (HAM-D) score from baseline to the end of week 3 was the primary outcome measure. Data were gathered from February 1994 to August 1998.
RESULTS: Thirty-eight patients completed at least 1 week on protocol, with 21 and 17 randomly assigned to the pindolol and control groups, respectively. After 3 weeks on protocol, partial response rates (i.e., minimum 50% decrease from baseline in HAM-D score and maximum absolute score of 15) for the pindolol (19% [4/21]) and control (24% [4/17]) groups were comparable. At 3 weeks, the pindolol and control groups demonstrated mean +/- SD decreases in HAM-D scores of 6.5 +/- 9.8 and 9.7 +/- 7.2, respectively. There were no significant differences in antidepressant response or side effects between the 2 groups.
CONCLUSION: These results do not support the efficacy of pindolol in augmenting clinical response to SSRIs in treatment-resistant depressed patient
[Interest of the use of pindolol in the treatment of depression: review].
AuthorsBrousse G, et al. Show all Journal
Encephale. 2003 Jul-Aug;29(4 Pt 1):338-50. Article in French.
Affiliation
CMPB, Service de Psychiatrie Adulte, CHU, rue Montalembert, 63003 Clermont-Ferrand.
Abstract
The principal stakes of depression treatment are to accelerate and enhance the clinical effects of antidepressant drug. The onset of antidepressant action of Serotonin (5HT) selective reuptake inhibitors (SSRIs) was attributed in part to the decrease in firing activity of serotonin neurons produced by the activation of raphe 5HT1A autoreceptors at the time of treatment initiation. Pindolol, an antagonist at somatodendritic pre-synaptic 5HT1A receptors has been investigated as a potential accelerator or potentialisator of antidepressant response. Six open label studies and 12 controlled studies were identified for revue. The first open-label pilot study was conducted by Artigas et al. They showed promising results with pindolol, both in the acceleration of antidepressant response and in improving the efficacy of antidepressant. On the basis of these results five open-label studies were conducted. The open label studies suggest that pindolol accelerate the antidepressant response of serotoninergics therapeutics. The augmentation of antidepressant response was not clearly demonstrated by these studies particularly in the treatment of refractory depression. For example, Dinan et Scott that found the addition of pindolol in association with SSRI therapy had a poor efficacy. In the twelve controlled studies, 4 tried to underscore the shortening of the onset and the augmentation of efficacy of SSRI by pindolol [Berman et al., Maes et al., Perez et al., Tome et al. ], 3 tried to underscore shortening of the onset [Bordet, Zanardi ] and 3 tried to underscore the augmentation of efficacy [Maes et al., Moreno et al., Perez et al. ]. One study tried to underscore the augmentation of efficacy of sleep deprivation by pindolol and another one the shortening of the onset of ECT. Six studies included depressive resistant patients. Three studies were carried out with fluoxetine, 1 with fluvoxamine, 3 with paroxetine, 1 with trazodone. Two -studies were investigated with several antidepressant treatments. The results of the studies indicate one acceleration of antidepressant response in 6 studies, one augmentation of efficacy in 5 studies. Two studies clearly demonstrate that pindolol may -augment and accelerate antidepressant response. Three studies did not confirm these observations. Several points can be examined. For pindolol: 3 authors have demonstrated that the effect of pindolol did not rely upon small antidepressant effect mediated by b-blockers properties, because anxiety was not predominantly improved by pindolol plus SSRI while depressive symptoms were clearly improved. On the basis of data issues from recent positron emission tomography (PET) studies, several authors suggested that the dose of pindolol used in most clinical trials (3 yen 2,5 mg day-1) might be insufficient to induce a substantial occupancy of 5-HTA receptors (Rabiner et al. It is possible that higher doses will show a more evident benefit. On the whole, pindolol seemed to be well tolerated. Adverse effects most commonly reported were increased irritability, insomnia and nausea. Pindolol had poor adverse effects in cardiovascular functions. The variation of the results of the controlled studies can be explained by different points: Firstly by difficulty to determine good criterion of resistance. The most simplistic definition of treatment resistance is the failure to achieve and sustain euthymia with adequate antidepressant treatment. Secondly by the fact that depressive patients who present antecedents of depressive illness seem to be worst responders to the association pindolol/serotoninergic antidepressant than patients suffering of first episode of depression. We observed one antecedent of depression in the group of resistant patients who were good responders to the association pindolol/antidepressant therapy. We observed three anterior episodes of depression in negatives studies of the association pindolol/antidepressant therapy. Thirdly by the fact that the failure of the antidepressant treatment at the time of earlier (or actual) episode seems to be a criterion for less responsiveness to the association of this antidepressant treatment with pindolol. In fact, the open label studies who demonstrated efficacy of the association between pindolol and serotoninergic therapy in major resistant depression were realized with new antidepressant molecule for the episode. Other controlled trials could confirm these facts. Most of the studies failed to retrace clearly the historicity of depression, and it may be interesting in future investigations to analyze the response of the association -compared to the status of the patient with the antidepressant therapy. Further perspective could be envisaged especially in the utilization of pindolol for the treatment of pathologies which are usually treated with a serotoninergic antidepressant -therapy. For example, the antagonist 5HT(1A) Way 100635 was experimented with success in animals in order to augment the efficacy of clomipramine in the treatment of chronic pain. In other respects several psychopharmacogenetics studies could be investigated to examine, for instance, the role of the 5-HT transporter and its implication in the response to pindolol and antidepressant association. In summary, pindolol accele-rates, and in some cases enhances the clinical action of antidepressant drugs. It appears that this augmentation strategy has more limited effect on treatment resistant patient but there is experimental evidence for using higher doses in future augmentation trial.
