Agents That Help Anger, Worry or Smoking – Off-Label Use of Antidepressants
By Alen J. Salerian, MD
“No way I’ll take that pill,” muttered the young man in his 30s, who had admitted himself voluntarily to the Psychiatric Institute’s adult treatment center because of cocaine abuse. “Why not,” I inquired, watching his protruding cheekbones and wondering whether his frail frame and skinny features were complications of his cocaine abuse. “I’m not depressed,” he answered. “I am not prescribing this medication for depression,” I said. “This one may help you with your drug addiction.” And that was not the only time that day I had offered a similar remark. “Yes, I am prescribing an antidepressant. Yes, I agree, you are not depressed and this medication may still help you.” The fact that antidepressants help people with depressive disorders is no longer disputable; however, what has also emerged during the last several decades has been the impressive evidence of how antidepressants benefit millions who are not 
depressed. In numerous controlled studies, antidepressants have proven their usefulness in such myriad psychiatric/medical conditions as tobacco dependence, phobias, obsessive-compulsive disorders, alcoholism, generalized anxiety disorders and premenstrual dysphoric disorder (1). From a biological perspective, all available antidepressants alter the brain’s neurotransmission of serotonin, dopamine and norepinephrine. Therefore, it is not surprising that antidepressants may also mediate a variety of such human functions as fear, anxiety and emotional memory regulated by the same system. Understandably, during the last decade the use of antidepressants has moved from the narrow indication for depression to a much larger spectrum of medical and psychiatric disorders. Historically and far too often, the clinical use of antidepressants has not been fully consistent with the current FDA-approved indications for these agents. For instance, selective serotonin reuptake inhibitors have only recently been approved for post-traumatic stress disorders, phobias and panic disorders; where as many experienced physicians have used SSRIs to treat the same conditions for years. Among the reasons many doctors cited for non-FDA use of antidepressants are the published scientific data supporting their use, their well-established safety record and the lack of FDA-approved efficacious agents for these same conditions. Recent psychiatric literature is rich with reports supporting using antidepressants for a variety of medical conditions ranging from chronic fatigue syndrome to tobacco dependence. However, many of these reports do not meet strict scientific criteria and often we, the treating physicians, are faced with a common dilemma – using a non-FDA approved yet potentially promising medication or maintaining status quo with a treatment-refractory patient.
depressed. In numerous controlled studies, antidepressants have proven their usefulness in such myriad psychiatric/medical conditions as tobacco dependence, phobias, obsessive-compulsive disorders, alcoholism, generalized anxiety disorders and premenstrual dysphoric disorder (1). From a biological perspective, all available antidepressants alter the brain’s neurotransmission of serotonin, dopamine and norepinephrine. Therefore, it is not surprising that antidepressants may also mediate a variety of such human functions as fear, anxiety and emotional memory regulated by the same system. Understandably, during the last decade the use of antidepressants has moved from the narrow indication for depression to a much larger spectrum of medical and psychiatric disorders. Historically and far too often, the clinical use of antidepressants has not been fully consistent with the current FDA-approved indications for these agents. For instance, selective serotonin reuptake inhibitors have only recently been approved for post-traumatic stress disorders, phobias and panic disorders; where as many experienced physicians have used SSRIs to treat the same conditions for years. Among the reasons many doctors cited for non-FDA use of antidepressants are the published scientific data supporting their use, their well-established safety record and the lack of FDA-approved efficacious agents for these same conditions. Recent psychiatric literature is rich with reports supporting using antidepressants for a variety of medical conditions ranging from chronic fatigue syndrome to tobacco dependence. However, many of these reports do not meet strict scientific criteria and often we, the treating physicians, are faced with a common dilemma – using a non-FDA approved yet potentially promising medication or maintaining status quo with a treatment-refractory patient. Chronic Fatigue Syndrome
Perhaps chronic fatigue syndrome, a somewhat common disorder – a medical condition with criteria of a six-month history of worsening fatigue and the presence of four of eight symptoms that include memory and sleep impairment as well as joint and muscular pain – illustrates the dilemma. Several studies support using nefazodone for people with chronic fatigue syndrome (2, 3).
Sleep Disorders
The use of antidepressants as sleep aids is a good example of how, even without FDA approval, we can successfully treat troubling symptoms. No antidepressant is currently approved for insomnia. Yet, for years, many physicians prescribed antidepressants such as Elavil, Desyrel and Sinequan to treat insomnia by pharmacologically exploiting the sedative properties of these medications.
Substance Abuse
Also increasing in the last decade is evidence supporting the relationship between subgroups of individuals with alcohol or drug dependencies and their biological propensity to a variety of psychiatric disorders (e.g., bipolar, mood, anxiety, attention deficit). Antidepressants may prove helpful for many of these conditions (7, 8).
The Downside of Off-Label Use
With every new approach there also is the potential of unforeseen complications. Recent medical history about the rise and fall of fen-phen to treat obesity illustrates the dangers associated with untested medical approaches. Several years ago, due to the increased risk of pulmonary hypertension, the FDA banned fen-phen only after many fatalities occurred. Mixing prescription drugs with non-prescription medications may even present a greater risk to our patients. Sadly, a common myth that medications considered natural only because they happen to the products of the earth are safe remains popular. Tobacco, cocaine and poison ivy are natural but are they harmless? The experience with St. John’s Wort, a highly popular antidepressants introduced as a natural supplement to help depression, may highlight some of the dangers associated with substances that are mistakenly identified as natural and safe. Since its introduction to the U.S. market, St. John’s Wort has been reported to cause serious complications due to interactions with other drugs. Of significance have been St. John’s Wort’s effects on calcium channel blockers and cyclosporine, an immunosuppressant commonly used to prevent organ rejection for transplant patients (1). Also not to be overlooked are the reported cases of St. John’s-induced hypomania (4, 5) or the potential risk of “serotonin syndrome” when St. John’s is combined with a standard SSRI. Recent psychiatric literature also reports mania induced by ginseng, a highly popular herbal remedy marketed as an energy booster (6).
Conclusion
While we must be careful about assuming that antidepressants may help all our patients, we may not be far from reconsidering the term antidepressant and perhaps entertain newer labels such as anti-anger agents, anti-worry meds, sleep aids, anti-smoking meds and so on.
References
- Susman E. Off-Label Use of Psychiatric Drugs. Primary Psychiatry. October 2000, Volume 7, No. 10.
- Goodnick P.J., Jorge C.M. Treatment of Chronic Fatigue Syndrome with Nefazodone. American Journal of Psychiatry. 1999; 156: 797-798.
- Hickie I. Nefazodone for Patients with Chronic Fatigue Syndrome. Aust NZ Journal of Psychiatry. 1999; 33: 278-280.
- Schneck C. St. John’s Wort and Hypomania [letter]. Journal of Clinical Psychiatry. 1998; 59: 258.
- O’Breasnail A.M., Argourch S. Hypomania and St. John’s Wort [letter]. Canadian Journal of Psychiatry. 1998; 43: 747.
- Gonzalez-Seijo J.C., Ramos Y.M., Lastra I. Manic Episode and Ginseng: Report of a Possible Case. Journal of Clinical Psychopharmacology. 1995; 15: 447-448.
- Cornelius J.R., Salloum I.M., Ehler G, et al. Fluoxetine in Depressed Alcoholics: A Double Blind, Placebo-Controlled Trial. Archives of General Psychiatry. 1997; 54: 700-705.
- Roy A. Placebo-Controlled Study of Sertraline in Depressed Recently Abstinent Alcoholics. Biological Psychiatry. 1998; 44: 633-637.