Benzodiazepines

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Dr. Philip Grossi
Sunday, 19 January 2014

In the January 2014 issue of the American Journal of Psychiatry, Mark H. Pollack, M.D. et.al. published an article about augmentation and switch strategies for social anxiety disorder. Initially 397 participants received sertraline (Zoloft). Of that number 181 were nonresponders and were randomly assigned to one of three groups: sertraline plus clonazepam, switch to venlafaxine (Effexor), or sertraline plus placebo.  At the termination of the study they found that the sertraline plus clonazepam group showed a greater improvement than the other two groups. The study authors conclude "the findings suggest that the clonazepam augmentation strategy provides relative benefits for sertraline nonresponders with social anxiety disorder."

I am highlighting this study because it is the first clinical trial data using benzodiazepines as an augmentation of SSRIs in anxiety disorder patients. This is surprising in light of the fact that this strategy is very likely the most common strategy used by practicing psychiatrists. It is important to convert the practice based strategy into one that is based on clinical trial data for many reasons including that it can now be incorporated into practice algorithms which will become more common in future evidence-based practice. I am also using this article as a bridge to issues regarding the use of benzodiazepines which are among the most commonly misunderstood drugs in all of medicine. This family of drugs includes widely used drugs such as clonazepam (Klonopin), alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan). All drugs in this family have four actions: anti-anxiety, anti-convulsant, anti-spasmotic, and soporific (sleeping agent). The PDR indication for the drugs' use is essentially a marketing decision by the pharmaceutical manufacturer. Roche the manufacturer of clonazepam studied clonazepam as an anti-seizure medication and the FDA approved it for use as an anti-convulsant. It took years for its value as an anti-anxiety agent to be appreciated. 

The benzodiazepines have been available since the 1960s.  They were initially embraced because they were much safer than other drugs in wide use such as the barbituates and older sedative hypnotics. Adverse effects such as addiction, cognitive side effects, amnestic behavior etc. were publicized in the 1970s and the drugs fell out of favor until about 1982 with the publication of an article demonstrating the effectiveness of alprazolam in panic disorder. Many doctors are still focused on these negative effects and do no believe that the drugs impact the core problem in anxiety.  This belief is not supported by the Pollack article cited above because many core symptoms were measured in that study and the change in symptoms was tracked with the Liebowitz Social Anxiety scale.

I believe the evidence supports my belief that the benzodiazepines are extraordinarily effective and safe agents. In the many thousands of patients I have treated with these drugs, I have yet to get anyone addicted or experience any major adverse event.  It is certainly true that they should almost never be used in individuals with an alcohol problem, should be used carefully in the elderly, cognitive side effects should be monitored, and doses kept to reasonable but effective limits which implies that a strategy be employed to handle tolerance which is common with all members of this drug family. 

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