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Psychopharmacology Newsletter Bay PPSSYYCCHHOOPPHHAARRMMAACCOOLLOOGGYY Area NEWSLETTER Volume 3, Issue 1 March, 2000 PINDOLOL AND SELECTIVE SEROTONIN REUPTAKE INHIBITOR Does the Addition of Pindolol Accelerate or Enhance the Response to Selective Serotonin Reuptake Inhibitor Antidepressants? By Talia Puzantian, PharmD, BCPP sion by blocking 5-HT1A autoreceptors nefazodone), 39 (70%) had a decreased laten- Adapted from Puzantian T and Kawase K in which, when activated, reduce normal firing, cy period of response. Increased efficacy Pharmacotherapy 1999;19(2):205-212. 5-HT synthesis, and 5-HT terminal release. when pindolol was added to a serotonergic ven with several antidepressants with What follows is a summary of available pub- regimen was not as much the focus of these differing mechanisms of action, many lished data that addresses this use. trials as was the effect on latency. However, 16 (59%) of 27 patients had increased efficacy Edepressed patients do not respond, The results of six open trials are summarized with pindolol augmentation. These prelimi- respond only partially, or experience a delay in in Table 1. Although it is difficult to make nary results suggested that the drug exerts a therapeutic response. It has been reported that definitive conclusions because these studies significant effect in terms of accelerating pindolol, a serotonin 1A (5-HT1A) autorecep- were not controlled or blinded and involved response to serotonergic antidepressants such tor antagonist, given in combination with only small samples, by putting the data togeth- as SSRIs or nefazodone, but not tricyclic anti- selective serotonin reuptake inhibitors (SSRIs) er one can see a trend favoring the positive depressants (TCAs). may accelerate and enhance their therapeutic effect of pindolol addition. Of 56 patients tak- effects. The proposed mechanism of action is ing serotonergic agents (SSRI, buspirone, that pindolol enhances 5-HT neurotransmis- Continued on page 2 TREATMENT CAN MODIFY RISK FACTORS FOR SUICIDE Jan Fawcett M.D. who committed suicide within one year of gency services where assessment by profession- Presented at a Grand Rounds in Community assessment with a comparison group yielded al staff was compared with self-report by the Psychiatry, San Francisco, CA several major findings. Among these findings patient on a series of psychological dimensions September 23, 1999 was the presence in suiciding patients of signifi- related to the suicide attempt. While profes- cantly increased comorbid panic attacks (62 per- sional staff reported their assessment of despair Certain clinical risk factors are more effective in cent versus 24 percent), significantly more and feeling overwhelmed, the patients reported assessing acute risk of suicide whereas others severe ratings of "psychic anxiety ", a signifi- severe anxiety and a state of emptiness (disso- are better at assessing chronic risk. Some of cantly higher incidence of "global insomnia" ciative anxiety?) leading up to their suicide these acute risk factors can be modified with (implying very severe insomnia), and acute attempt. A recent study of inpatient suicide treatment if they are recognized. Findings from moderate severity of alcohol abuse. These find- records found the presence of severe psychic our research indicates that most of the standard ings were recently partially replicated by Hall et anxiety, agitation, or both in 79 percent of risk factors mentioned in textbooks are probably al., who studied 100 consecutive cases of suicide patients within one week of their suicide. chronic risk factors. For this reason, recogni- attempts severe enough to require hospital tion of acute risk factors is important in direct- admission. On the basis of a standardized inter- These findings, taken together, suggest that ing timely interventions. view of these patients, 90 percent reported severe anxiety or agitation symptoms occurring severe anxiety and 80 percent reported the in patients with depression may be important What information is available to us concerning occurrence of panic attacks shortly prior to their acute risk factors to assess and address thera- acute risk factors in suicide? The Collaborative suicide attempt. A recent Swiss study reported peutically. While there are no controlled studies Depression Study which compared 13 patients on 30 consecutive suicide attempts seen in emer- to establish that the rapid treatment of severe anxiety symptoms reduces suicide risk, the author's clinical experience suggests that this is INSIDE THIS ISSUE the case. We know from clinical experience that if addressed aggressively, anxiety symptoms can Comparison of Zolpidem and Zaleplon . .2 be rapidly ameliorated. Controlled studies on County Insert . .3 this question would be very difficult to conduct, Reboxetine . .5 but research in this area is much needed. Continuing Medical Education . .6 Continued on page 2 Bay Area Psychopharmacology Newsletter PINDOLOL AND SEROTONIN REUPTAKE INHIBITOR ANTIDEPRESSANTS SUICIDE: TX CAN MODIFY RISK FACTORS Continued from page 1 Continued from page 1 TABLE 1 OPEN TRIALS Another risk factor for suicide that may be treatable is the trait of impulsivity. Impulsivity is a trait asso- STUDY DURATION REGIMEN + PINDOLOL 2.5 MG TID RAPID ONSETa GREATER EFFICACYa ciated with the diagnoses of bipolar disorder, bor- (WKS) derline and antisocial personality disorders, and 2 Paroxetine 20mg/d 5/7 NA alcohol or substance abuse histories. A number of 2 Various NA 6/8 studies have shown that impulsive, violent, suicidal 4 Paroxetine 20mg/d 7/9 NA behavior is associated with measures of low sero- 4 Various NA 10/19 tonin function in the brain. Recently, a number of 4 Buspirone 30mg/d 9/10 NA studies from Europe have suggested that mainte- 4 Desipramine 150mg/d 0/5 NA nance treatment with lithium carbonate may signif- 4 Trimipramine 150mg/d 0/5 NA icantly reduce the likelihood of suicide in patients 4 Fluvoxamine 100mg/d 3/10 NA with both bipolar and unipolar affective disorders. 4 Nefazodone 100mg/d 15/20 NA There is evidence to suggest that lithium carbonate acts by enhancing serotonin function at the second aBased on 50% or greater improvement in HAM-D score (by week 1 or 2 for rapid onset) messenger level in the brain. These data suggest the Five randomized, double-blind, placebo-controlled studies with a total of 330 patients have possibility that lithium carbonate maintenance been published to date, with mixed results (see Table 2). Taken together, the data suggest that treatment, in addition to its stabilizing effect on pindolol is effective in some patients in accelerating the response to serotonergic antidepres- mood in bipolar disorder, may specifically address sants. However, whether there are predictors of favorable response remains to be seen, and fur- the behavioral dimension associated with suicide in ther study in this regard is certainly needed. For example, in one study, patients who were depressed patients. For instance, one study has referred mainly from primary care had more rapid response than those referred by psychiatry. shown that patients maintained on lithium carbon- Similarly, another study failed to show a more rapid onset with pindolol, although patients may ate had lower suicide rates even if their bipolar dis- have had more chronic disease and been more difficult to treat. order was not completely responsive to the treat- ment. The growing body of clinical data with TABLE 2 respect to lithium and the prevention of suicide O OF STUDY DURATION N . REGIMEN + PINDOLOL RAPID ONSETa GREATER EFFICACYa point to the possibility that this treatment may (WKS) PATIENTS 2.5 MG TID address a specific behavioral dimension associated 6 111 Fluoxetine 20mg/d No Yes with suicide, possibly through its effect on serotonin 4 33 Trazodone 100mg/d NA Yes function. Adding to this possibility is the observa- 6 80 Paroxetine 20mg/d Yes/no NA tion that patients taken off of lithium seem to have 6 43 Fluoxetine 20mg/d No No increased suicide risk. 4 63 Paroxetine 20mg/d Yes Yes We have reviewed data suggesting that severe anx- aBased on 50% or greater improvement in HAM-D or MADRS (by week 1 or 2 for rapid onset) iety/agitation symptoms occurring in depression are acute risk factors for suicide, and that they may be b Four patients received pindolol 5mg bid instead of 2.5mg tid; five patients received placebo bid amenable to aggressive anxiolytic treatment. We instead of tid also reviewed the association of impulsivity with Evidence from these studies indicate that pindolol accelerates and perhaps enhances therapeutic suicide and depression, as well as the data suggest- effects with antidepressant drugs that act by way of serotonin neurons, specifically SSRIs. The ing that lithium carbonate maintenance may reduce difficulty in extrapolating these data into real world practice is due to lack of information on suicidal behavior. In this report, I have tried to expected response rates, predictors of response, and controlled trials comparing this with other emphasize the importance of recognizing acute risk augmentation strategies such as lithium or triodothyronine. In light of the fact that pindolol is fair- factors for suicide and, when possible, trying to ly safe and well tolerated, has rapid onset of response, is limited by few contraindications, and is reverse factors with treatment. This approach could relatively inexpensive, it may be a sensible and valuable addition to the options for treating depres- improve the ability of clinicians to assess suicide sion. risk and prevent suicide in their
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