Abstract
Bupropion-induced hypomania in a patient with unipolar depression
Antidepressant-induced switch episodes of hypomania/mania can occur in patients with bipolar depression [1]. Such switch episodes occur much less commonly in unipolar depression [2]. Although all antidepressants have been implicated, bupropion is thought to carry much less risk [3], [4]. Contrary to this belief, we present a case that highlights bupropion-induced hypomania in a patient with unipolar depression. This is, to our knowledge, the first such reported case.
The patient, a 31-year-old woman, had been under our treatment due to a 3 month history of depressed mood, impaired concentration, worthlessness, disturbed sleep and loss of appetite. Past history was suggestive of chronic depression successfully treated with antidepressant monotherapy. No previous trial of mood stabilizers was reported. The patient admitted to two previous suicide attempts but denied any current suicidal thoughts. The patient did not report any previous episode of hypomania/mania. Historically or at the time of assessment there were no delusions or hallucinations. The patient had an extensive family history of psychiatric problems. Her biological mother and sister as well as all of her children were suffering from unipolar depression. There was no family history of bipolar illness. General physical examination and all relevant laboratory investigations including thyroid function were within normal limits. The patient was diagnosed with unipolar depression and started on bupropion (Wellbutrin XL, GlaxoSmithKline, Memphis, TN, USA) 150 mg day−1.
When seen at follow up after 3 weeks of treatment, the patient reported significant improvement in her symptoms of depression. She reported euthymic mood, improvement in concentration, no anhedonia and some improvement in sleep and appetite. The patient reported no side-effects from medications. But 5 weeks after starting bupropion the patient reported elated mood, increased energy level, decreased need for sleep, and racing thoughts. During assessment the patient seem restless and was pacing all around the interview room (psychomotor agitation). She reported no grandiose or other delusions but scored 9 on the Altman Self-Rating Mania Scale [5] (score >6 suggests hypomania or mania), and the patient met DSM-IV criteria for hypomania. We decided to stop bupropion.
Two weeks later the hypomanic symptoms subsided (Altman Self-Rating Mania Scale score = 5) and the patient's mood reverted to euthymia. It was obvious that the patient had had an episode of medication-induced hypomania. On follow up the patient continues to be treated for unipolar depression only, with a history of medication-induced hypomania.
In light of the aforementioned findings we emphasize the need for prescribers to maintain a high index of suspicion regarding medication-induced hypomania, even with regard to bupropion, and even when the patient has unipolar depression only.
Preventing alcohol abuse and suicidal behaviour among college students
Suicide is a serious problem that can affect teenagers and young adults at an age when serious mental illness first manifests itself and often goes undiagnosed. Suicide is the third leading cause of death among 15–24-year-olds in the USA and the second leading cause of death among college students after car accidents [1]. College years are a crisis for many students. On campus, they are exposed to freedom and choices in their personal life to a much greater extent than in high school days. Recent data suggest that students between the ages of 18 and 24 consume on average nine drinks per week [2]. The same research reported that 30% of males students consumed more than 21 drinks per week and almost 20% of females students consumed more than 14 drinks per week. Of drinkers, 28% identified as heavy drinkers and 72% were moderate drinkers, consuming approximately 11 drinks per week. Alcohol is involved in 66% of college student suicide, in 90% of college rapes, and in 95% of violent crimes on campus [3]. Acute alcohol use was identified as a factor that can potentially precipitate suicidal behaviours through impairment of problem-solving and impulsivity [4]. Prolonged periods of alcohol abuse increase the likeliness of depressive symptoms. A recent study of college students found significant relationships between past alcohol use and past suicide attempt(s) and between past binge drinking and past suicidal behaviour and ideation [5]. According to university counsellors and psychologists, alcohol consumption is the greatest single problem that universities must address. This requires not only reducing alcohol consumption, but also changing the behavioural norms of college students. Intervention programmes need to be designed to increase student awareness of alcohol-related problems in order to change their attitudes and beliefs and to reduce suicidal behaviour. Suicide prevention measures should target specific groups, such as sororities, fraternities and sports teams supporting peer communication in the hope of changing students’ social norms about alcohol use. Changing the perception of the normative nature of alcohol use among college students should decrease students’ level of use and, consequently, suicidal behaviour. In addition, there is a clear need to identify students with psychological difficulties. The warning signs of mental illness can be difficult to spot in the context of college, where unusual sleeping patterns, drug use and binge drinking are common. Greater attention to alcohol and drug abuse and suicidal behaviour on college campuses is urgently needed.
Successful re-challenge with clozapine following development of clozapine-induced cardiomyopathy
Clozapine, used in treatment-resistant schizophrenia, has several serious and potentially fatal cardiac complications. In particular, the development of myocarditis and cardiomyopathy secondary to clozapine has been reported in numerous cases in the literature [1]. In practice, if one of these complications does occur, we cease clozapine and use other antipsychotic agents. Previously re-challenge with clozapine had not been considered. There have been case reports of successful re-challenge with clozapine following myocarditis, and one case report of unsuccessful re-challenge with clozapine [2]. We report here a case of successful clozapine re-challenge following the development of cardiomyopathy in chronic treatment-resistant schizophrenia.
The patient was a 33-year-old man with mild intellectual impairment and a chronic history of treatment-resistant schizophrenia. He had no history of cardiac disease and was physically fit. He was started on clozapine in 1996 after non-response to other antipsychotics with the dose titrated to 600 mg. He demonstrated significant improvement in his mental state and general level of functioning. In 2001, during routine cardiac monitoring, the echocardiogram performed was normal. In December 2004 a routine echo indicated a mildly dilated left ventricle (LV) with mild LV dysfunction and ejection fraction (EF) 45–90%. On cardiology review the diagnosis was made of probable mild cardiomyopathy that may be chronic because the changes were mild and the patient remained asymptomatic. The patient was continued on clozapine and reviewed by a cardiologist 6 months later. A repeat echocardiogram at this time demonstrated a significant worsening of his LV function, with EF 35-40% and increased LV dilatation. It was felt that although clozapine could not be the sole cause, it was likely a contributing factor. The patient was started on angiotensin-converting enzyme-I (ACE-I; ramipril 5 mg) as well as digoxin 250 µg and later a beta-blocker (carvedilol). His clozapine was ceased in October 2005 and he was started on aripirazole. Throughout this period the patient demonstrated no cardiac symptoms. But in December 2005 at routine outpatient review the patient reported bilateral peripheral oedema and dizziness and further cardiology opinion was sought. The patient's symptoms resolved over a few days. Follow-up echocardiograms returned to normal and his cardiac medications were ceased in December 2006. Following the cessation of clozapine the patient's mental state deteriorated. In July 2007 during a further admission to hospital, the possibility of clozapine re-challenge was raised. It was clear that the patient had deteriorated significantly since clozapine was ceased: there had been frequent hospital admissions, increasingly aggressive behaviour and more symptomatic distress. Following discussion with the patient, his family, the treating cardiologist and the treating psychiatric team it was felt that the benefits of recommencing clozapine outweighed the risk of developing cardiomyopathy again. Following a normal echocardiogram, electrocardiogram and routine bloods the patient was restarted on clozapine, titrated to a dose of 600 mg. He was also started on prophylactic ACE-I (ramipril 5 mg). Repeat echocardiogram after 1 month of treatment excluded any deterioration in cardiac function (LVEF 58%) and since that time his LVEF has remained within normal limits. His mental state has improved significantly and he has been followed closely by cardiology with regular echocardiograms.
The development of cardiomyopathy following clozapine use in treatment-resistant schizophrenia has been documented in the literature, but the incidence remains unclear. The difficulty in diagnosing a definitive causal relationship due to non-specific signs and symptoms makes interpretation of case reports difficult. It is understood that significant cardiac complications such as myocarditis and cardiomyopathy are most likely to develop within the first few months of staring clozapine, but the development of cardiomyopathy has been reported after several years [3]. The pathophysiology remains unclear but postulated aetologies include an IgE-mediated hypersensitivity reaction, type 3 allergic reaction and direct toxic effects [1], [4]. Furthermore, the outcome of re-challenging a patient with clozapine following the development of cardiomyopathy remains unknown. Whether this reflects a similar underlying process is unknown. The present case demonstrates a successful case of clozapine re-challenge following the development of cardiomyopathy in chronic treatment-resistant schizophrenia. In the present case it was felt that the benefits to the patient of re-starting clozapine outweighed the risks. The patient will continue to require close cardiac monitoring but this case demonstrates, however, that in selected patients, re-challenge with clozapine following the development of cardiac side-effects could be considered.