Manufacturer: Brand WyethCategory: Fat burnersSubstance: sibutraminePackage: 10 pills
The temporal relationship between sibutramine intake and onset of behavioral changes as well as the decrease in manic symptoms with cessation of sibutramine and initiation of anti-manic pharmacotherapy led us to suspect the role of sibutramine in the pathogenesis of manic episode. It could be hypothesized that sibutramine may induce mania in predisposed individuals by acting in a similar way with other selective serotonine reuptake inhibitors (SSRIs) [ 14 ]. In the 1980s sibutramine was initially intended as an antidepressant drug [ 3 ]. In the 2000s antidepressant-associated mania has been linked to all major antidepressant classes in a subgroup of 20-40 % of bipolar patients [ 18. 19 ]. Bipolar spectrum incorporates classic bipolar disorder (manic + depressive episode), bipolar II disorder (hypomanic + depressive episode), and bipolar III disorder that is not an official diagnosis recognized by psychiatric associations. Although we will not find bipolar III disorder mentioned in the International Classification of Diseases (ICD-10) or Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), psychiatric professionals use the unofficial diagnosis of bipolar III disorder to describe patients who have experienced manic or hypomanic episode due to antidepressant treatment [ 20 ]. The serotonin transporter gene is a candidate to be associated with antidepressant-associated mania in some patients [ 21 ]. The serotonin transporter gene demonstrates a polymorphism within the promoter region (5-HTTLPR) with two allelic forms -the long and the short variants. Since 5-HTTLPR polymorphism is considered as a predictor of abnormal response to antidepressants in vulnerable to bipolar disorder patients, a correct diagnosis of bipolarity and detailed family history for affective disorders should be done before the beginning of sibutramine treatment. It is essential mainly for short variant of 5-HTTLPR carriers [ 19 ]. As chronic sleep deprivation can precipitate the manic episode, insomnia (a very common side-effect of sibutramine) might exacerbate manic symptoms in our vulnerable patient. It was also hypothesized that individuals can engage in overeating for the purpose of regulating their mood [ 22 ]. Therefore, bipolar patients may overeat to “self medicate” their affective symptoms, and suppression of overeating and/or weight loss might therefore trigger the onset or exacerbation of the mood symptoms. It is also possible that the weight loss might also be associated with release of toxins, including drugs that might have mood destabilizing effects [ 22 ].
Although the neuropsychiatric side effects of sibutramine have not yet been completely elucidated, there is accumulating literature on a variety of psychiatric disturbances caused by sibutramine. Further studies are required to clarify the relationship between sibutramine and episodes of psychiatric disorders including mania. Sibutramine, as an antiobesity drug was approved in the USA in 1997 and in the European Union in 1999, but recently followed the example of another antiobesity drug -rimonabant (an inverse agonist for the cannabinoid receptor CB1) that was removed from all markets in the European Union [ 23 ]. There was concluded that the risks of cardiovascular complications of sibutramine were greater than its benefits. Potential risks associated with the sibutramine treatment of obesity warn physicians to be alert not only to cardiovascular events but also to psychiatric adverse effects. Therefore a careful assessment of patient’s mental state together with detailed family psychiatric history should be done before beginning sibutramine treatment. If patients present a first episode of psychosis, mania, or other psychiatric disorder, they should be investigated thoroughly while sibutramine is being withheld [ 3 ]. It is important to obtain information about vulnerability of the patient to psychiatric disorders and whether eventual symptoms were due to a primary psychiatric disorder or to a drug-induced episode. In patients with weight gain while on antipsychotic medications (e.g. olanzapine treatment), sibutramine, if not managed appropriately, could conceivably exacerbate psychotic episode symptoms or trigger its relapse. Physicians should also remember that use of sibutramine is contraindicated not only in patients with a history of coronary artery disease, heart failure, arrhythmias, cerebrovascular disease, inadequately controlled hypertension, bulimia/anorexia nervosa, pregnancy, lactation, severe renal or liver dysfunction, narrow angle glaucoma, but also in patients treated with monoamineoxidase inhibitors (MAOIs), selective serotonine reuptake inhibitors (SSRIs) or certain migraine drugs as triptans, because of potential risk of serotonin syndrome. Thus, a 2-week interval is required after stopping MAIOs -before treatment with sibutramine, and after stopping sibutramine -before treatment with MAOIs [ 3 ].