Faculty Bibliography

Torsade de pointes (TDP) is a life-threatening ventricular arrhythmia characterized by a polymorphous QRS complex on an electrocardiogram (EKG). It is associated with a preceding prolonged ventricular repolarization represented by a lengthened QT interval. Although commonly induced by drugs, particularly in elderly women with ischemic heart disease, medication-induced TDP can occur in patients without a history of any cardiac problems. Drugs associated with TDP include Group la and III antiarrhythmics, phenothiazines, butyrophenones, and heterocyclic antidepressants. TDP may also be caused by electrolyte or metabolic abnormalities, central nervous system disease, cardiac disease, congenital syndromes, or toxins. Clinically, ziprasidone is as effective as haloperidol for the treatment of acute, positive symptoms of schizophrenia, and is effective in long-term relapse prevention. It is also approved for treating acute mania and mixed episodes associated with bipolar disorder. While it is generally not sedating and has a low likelihood of causing weight gain, some adverse effects that are associated with ziprasidone include migraine headaches, tardive dyskinesia, galactorrhea, prolonged erections, and mania. The following is a report of ziprasidone-induced TDP.

Depression and cardiovascular disease are associated with each other. In general, selective serotonin reuptake inhibitors (SSRIs) are safe and effective antidepressants in those with coronary heart disease. Despite this, unanticipated drug-drug interactions may sometimes occur. The following is a report in which coadministration of the SSRI paroxetine resulted in digitalis intoxication.

Aripiprazole is an atypical neuroleptic indicated for the treatment of schizophrenia and acute manic and mixed episodes associated with bipolar disorder. A potent dopamine partial agonist, aripiprazole acts as an antagonist at dopamine (D) receptors under hyperdopaminergic conditions and as a D-sub-2 agonist under hypodopaminergic conditions. It has been theorized that dopamine partial agonists may be able to stabilize the dopaminergic system without inducing a hypodopaminergic state, thereby reducing the risk of side effects associated with pure blockade of dopamine receptors. In addition to these effects, aripiprazole also acts as a partial agonist at serotonin (5-HT)-sub-1asymptotic-to > and as an antagonist at 5-HT-sub-2asymptotic-to > receptors. The most commonly reported side effects in association with use of aripiprazole include insomnia, anxiety, headaches, nausea, vomiting, and somnolence. The following is a report of aripiprazole-associated seizure.

Hypothermia is a life-threatening emergency. Besides exposure to cold, causes of hypothermia include sepsis, hypothyroidism, hypoglycemia, or drug overdose. Classically, neuroleptics have been associated with hyperthermia, particularly in relation to the neuroleptic malignant syndrome (NMS). The February 1999 'Psychopharmacology Journal Watch' cited an article on neuroleptic-associated hypothermia. At the time, the authors reported on 10 cases of neuroleptic-associated hypothermia reported to the drug safety surveillance program of the German Federal Institute for Drugs and Medical Devices between 1988 and 1997. The reports involved 6 women and 4 men, ranging from 19-86 years of age (average age = 50 years). In all cases, neuroleptics were given for either paranoid psychosis or schizophrenia. The substances involved included various neuroleptics, some of which are not available in the United States. Nine of the patients were treated with neuroleptics (clozapine, risperidone, chlorprothixene, zotepine, levomepromazine, and pipamperone) that are more potent antagonists at the serotonin 5-HT2 receptor than at the dopamine D2 receptor. In most cases, there was a period of several days from initial exposure to medication to the onset of hypothermia. The following is a report of hypothermia in a patient taking the atypical neuroleptic risperidone in combination with the selective serotonin reuptake inhibitor paroxetine.

Topiramate is a sulfamate-substituted monosaccharide indicated for adjunctive treatment of adult partial-onset epilepsy. It blocks voltage-gated sodium channels, enhances y-aminobutyric acid (GABA) via its actions on the GABAA receptor, antagonizes the kainate (aminomethyl)phosphonic acid (AMPA) subtype of the glutamate receptor, and inhibits carbonic anhydrase. Due to its ability to suppress appetite and cause weight loss, it has gained increasingly widespread use among clinicians as a treatment for psychotropic-induced weight gain, binge-eating disorder, and even bulimia nervosa. Other research suggests that topiramate may also be effective for the treatment of posttraumatic stress disorder, obstructive sleep apnea, opiate and benzodiazepine withdrawal, kleptomania, alcohol dependence, self-injurious behavior, aggression, nonparaphilic sexual addiction, promotion of scar healing, and treatment of olfactory hallucinations. In studies of epilepsy, the most frequently reported side effects of topiramate were somnolence, dizziness, paresdiesias, ataxia, speech disorders, cognitive dysfunction, psychomotor slowing, headache, nausea, nystagmus, tremor, fatigue, gastrointestinal upset, visual disturbances, and renal calculi. Dose-related side effects include difficulty concentrating, tremor, mood lability, fatigue, confusion, and weight loss. Reports also indicate topiramate-induced bilateral angle-closure glaucoma, topiramate- induced depression, and oligohidrosis and metabolic acidosis. The following is a report of topiramate-induced bilateral angle-closure glaucoma in a woman prescribed topiramate off-label for mood stabilization. (journal abstract)

Presents the case of a 40-year-old man who developed a psychotic episode and was treated with risperidone 8 mg/day, after which he developed a hypokinetic-rigid syndrome. Biperiden 2 mg was added; a major depressive episode soon followed. Mirtazapine 45 mg/day was added to his medication regimen, and when subsequent outpatient treatment failed, he was admitted to a psychiatric day clinic. The patient improved. However, 6 weeks after the initiation of this combination therapy he began to complain of acute aching in his left leg and respiratory problems. Later, the patient's depression remitted, vocational rehabilitation was started, and the patient was discharged in a euthymic state 8 weeks after the thromboembolism. This case is the first published report of both thromboembolism and rhabdomyolysis during combined therapy with risperidone and mirtazapine. The pathophysiologic mechanism that explains this adverse event is unknown but could involve a pharmacodynamic interaction between the two agents, both of which are antagonists at 5-HT-sub-2 receptors. Clinicians who prescribe the combination of mirtazapine with risperidone ought to be aware of the possibility of this serious complication.

Attention-deficit/hyperactivity disorder (ADHD) is a clinical disorder that may be confused with other medical and psychiatric conditions, due to overlapping symptoms. Often, symptoms suggestive of ADHD may be explained by other diagnoses. Medical 'mimics' one should consider when diagnosing a patient with ADHD include sleep deprivation, chronic and acute illness, medication effects, cognitive deficits, and other psychiatric disorders such as Asperger's syndrome, substance use disorders, and mood disorders. ADHD in both children and adults is also associated with academic performance problems, such as learning disabilities and executive functioning deficits. Learning disabilities such as math and spelling deficits are more common in children, although both age groups experience difficulties with reading and listening comprehension. Executive deficits in response inhibition and working memory have been demonstrated to be predictive of impairment in virtually every major life activity. Evaluation of both children and adults with ADHD requires screening for comorbid medical, psychiatric, and learning disorders; executive functioning; and history of school impairment. In this monograph, Russell A. Barkley, PhD, reviews the comorbidity of adult attention-deficit/hyperactivity disorder (ADHD) and learning and executive function disorders. Next, Timothy E. Wilens, MD, discusses differential diagnosis of ADHD as well as the prevalence of psychiatric comorbidity in adult ADHD. Finally, Lenard A. Adler, MD, reviews Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for adult ADHD and reviews the diagnostic and symptom assessment instruments available for the evaluation of ADHD in this population. (journal abstract)

Aripiprazole is an atypical neuroleptic indicated for the treatment of schizophrenia and acute manic and mixed episodes associated with bipolar disorder. The most commonly reported side effects in association with use of aripiprazole include insomnia, anxiety, headaches, nausea, vomiting, and somnolence. This article presents the first published reports of aripiprazole-induced new-onset diabetes mellitus.

Reports the case of a 42-year-old physically healthy woman with a 12-year history of depression and alcohol abuse received a prescription for citalopram 40 mg/day. Despite near abstinence from alcohol for 6 months, she continued to experience episodes of depression and hypomania, consistent with a diagnosis of bipolar type 2 disorder. She had no prior history of auditory, visual, or tactile hallucinations. Lamotrigine 25 mg/day was initiated, and then increased to 50 mg/day after 2 weeks. The patient reported improved mood without any side effects. After another 2 weeks, lamotrigine was increased to 100 mg/day. At this point, the patient's sleep became disturbed, with frequent waking and vivid dream-like experiences during which time the patient was not fully asleep. Five days later, she experienced visual hallucinations involving seeing her daughter and her nurse. She also reported headaches and hypersensitivity to noise. After lamotrigine was reduced to 50 mg/day, the hallucinations subsided over the next 48-72 hours.

Previous reports have documented an association between the macrolide antibiotics clarithromycin and erythromycin with depression, mania, and acute psychosis. This is the first published report of an association between another macrolide antibiotic, azithromycin, and psychotic depression and catatonia. The patient is an 81-year-old woman with a medical history notable for eyelid carcinoma, which was treated 1 year previously with surgery and radiotherapy, and hypertension, which was treated with spironolactone and chlortalidone.