Dr. Grossi's Blog
Over the past several weeks a series of patients have presented in which the distinction between mourning and major depressive disorder was required in order to properly inform treatment decisions. The mourning period length shows much individual variation but is almost always completed in five or six months. Mourning is regularly triggered by the loss of a loved person or some abstraction such as freedom, a meaningful goal, health etc. The work of mourning is carried out piecemeal. The memories of the lost person are recalled and appropriate emotions are experienced around those recollections, piece by piece. When complete, they are assembled like a jigsaw puzzle and can be put away on a shelf. If the mourning period exceeds five or six months, then mourning needs to be distinguished from depression to make correct treatment decisions.
What are some of the factors that help to distinguish mourning from depression? The feeling state in mourning is one of loss or emptiness which washes over the person in waves whereas in depression there is a more persistent painful dejection, lowering of self-regard, and expressions of self-reproach, self-reviling, and inability to experience happiness, loss of capacity to love or experience pleasure. In mourning there are intervening periods of happiness or even humor and self esteem is usually preserved. This is not so in depression. If depression is present in mourning, it is usually centered on the departed and possiblly joining him/her. In depression those thoughts are focused on taking one's own life because of the painful lowering of self-esteem.
Robert Gibbons and John Mann published a meta-analysis of seventeen randomized, placebo-controlled studies involving 8,027 participants. They reported that varenicline (Chantix) improved tobacco abstinent rates when compared to placebo and buproprion (Wellbutrin). They also reported that valenicline was not associated with adverse psychiatric events, i.e., there was no greater incidence of depression, agitation, mood problems, or suicidal ideation in those treated with varenicline than those on placebo. The authors also evaluated a large data set from DOD involving 35,000 smokers. In this study in both the overall sample and the portion who had comorbid psychiatric diagnoses the smokers who received valenicline were awarded fewer diagnoses of psychiatric disorder than those who received nicotine replacement therapy. There is not evidence in these studies of new or emerging psychiatric symptoms.
In 2009 the U.S. Food and Drug Administration placed a black box warning for varenicline regarding adverse psychiatric events. This has placed clinicians in the unenviable position of proving a negative. i.e., psychiatric symptoms are not associated with the medication. The initial trials run by Pfizer, the manufacturer, to seek approval from the FDA excluded participants with a psychiatric diagnosis. After the drug was released and used in the community, depression, anxiety, mood disorders, and suicidal ideation and action were observed and the drug was blamed and the press sensationalized and inflated the adverse effects leading to caution on the part of prescribers. Had the initial trials not excluded those with a psychiatric diagnosis, then they could have been evaluated with a control group.
As a clinician I am always balancing the risks, continuing smoking, with the benefits, decreased mortality from many causes. The risk is high and the benefit is substantial. The data are clear. A large proportion of smokers who want to quit and use pharmacological cessation aids can quit and psychiatric symptoms remain relatively stable during and after quitting. I advise that any increase in anxiety, depression, irritability etc. are transient and mild. I do advise them to expect nausea and vivid dreams which I treat if troublesome.
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.