Faculty Bibliography

Topiramate is a sulfamate-substituted monosaccharide approved for monotherapy in partial seizures, generalized tonic clonic seizures, and migraine prophylaxis. It blocks voltage-gated sodium channels, enhancesgamma -aminobutyric acid (GABA) via action on the GABA-sub(A) 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, topiramate 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 (PTSD), obstructive sleep apnea, opiate and benzodiazepine withdrawal, kleptomania, alcohol dependence, self-injurious behavior, aggression) non paraphilic sexual addiction, olfactory hallucinations, and even for the promotion of scar healing.

The porphyries are a group of bullous disorders caused by abnormalities in the synthesis of heme. Various enzyme deficiencies lead to accumulation of porphyrin precursors. Clinically there are three main categories of which the variegate subtype is characterized by acute episodes and skin changes. Acute cases are characterized by abdominal pain and neuropsychiatric disturbances. Skin changes include acute flares with erythema, edema with pain, and burning. A second pattern has skin fragility with blisters, erosions, and scars. According to the American Porphyria Foundation, drugs considered unsafe for use in porphyria include anticonvulsants, such as phenytoin, carbamazepine, and valproic acid; barbiturates, oral contraceptives, calcium channel blockers, clonazepam, and sulfonamide-antibiotics. (journal abstract)

This article is a report of serotonin syndrome resulting from an interaction between cyclobenzaprine and the serotonin norepinephrine reuptake inhibitor duloxetine. This article presents a case study of a 53-year-old man with a history of multiple low-back surgeries. He had a history of chronic pain and depression, for which he was receiving duloxetine 60 mg/day, pregabalin 75 mg BID, bupropion 300 mg/day, and oxycodone or hydromorphone as needed for pain. The temporal sequence of events described in this article is consistent with serotonin syndrome resulting principally from an interaction between cyclobenzaprine and duloxetine.

This article is the first published case of erythema multiforme minor in association with the second-generation antipsychotic quetiapine. This article presents a case study about a 21-year-old woman with 'school refusal' and home withdrawal for 1 year. This case study is consistent with quetiapine-induced erythema multiforme minor.

Atomoxetine is a norepinephrine reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. In randomized controlled trials, approximately 70% of children and adolescents with ADHD without comorbidity responded as measured by reduced scores on a variety of ADHD scales. Prior to being studied in ADHD, atomoxetine was known as tomoxetine and studied as an antidepressant. In those trials, as well as in a recent case report atomoxetine induced mania, a finding consistent with antidepressant activity. The following is the first published report of sialolithiasis in association with atomoxetine. (journal abstract)

Modafinil is a novel psychostimulant that is Food and Drug Administration-approved for the treatment of excessive daytime somnolence associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, or shift work sleep disorder. Among its pharmacologic properties, modafinil enhances glutamate neurotransmission. In contrast to other stimulants, modafinil does not cause elation or euphoria in healthy volunteers or in substance abusers. In fact, one report suggests that modafinil may be effective for the treatment of amphetamine craving and dependence, while another report indicates that it may be useful in the treatment of cocaine dependence. Because of this lower abuse potential, modafinil is a Schedule IV prescription, allowing multiple refills and prescriptions by phone. Among the most common side effects associated with modafinil in premarketing trials were headache, nausea, anxiety, and insomnia. (journal abstract)

Tactile hallucinations of insects, snakes, or other vermin crawling on the skin is known as formication. Overdoses of the norepinephrine-dopamine reuptake inhibitor bupropion have been associated with formication. The following is a report of two cases of formication occurring in association with therapeutic doses of bupropion. In the first case, a 39-year-old African-American woman suffered from posttraumatic stress disorder, major depressive disorder (MDD), and cocaine dependence in full remission for 10 months. There was no history of psychosis or mania. Her medication regimen consisted of buspirone, felodipine, fluoxetine, hydrochlorothiazide, omeprazole, simvastatin, sulindac, and psyllium powder. Bupropion sustained release (SR), titrated over 2-3 weeks to 200 mg BID, was added to augment fluoxetine. Within 3 weeks, the patient complained of bugs crawling on her skin, noting that, when using cocaine, she had similar experiences. Her symptoms abated after her total daily dose of bupropion SR was reduced to 300 mg. In the second case, a 40-year-old white woman had recurrent MDD with no history of psychosis or mania. She was taking levothyroxine, loratadine, montelukast, ranitidine, riboflavin, butalbital as needed for migraines, gabapentin or trazodone as needed for insomnia, and ibuprofen. Bupropion SR was initiated and then titrated over 3 months to 200 mg BID. The depression remitted. However, 11 months into treatment, the patient admitted that soon after increasing her dosage of bupropion to 200 mg BID she developed continuous, mild, tactile hallucinations like bugs crawling on her skin. Her tactile hallucinations resolved after the total daily dose of bupropion SR was reduced to 300 mg. The cases described above are consistent with bupropion-associated formication. Clinical caution is advised.

The occurrence and duration of paroxysmal atrial fibrillation are influenced by vagal tone. The selective serotonin reuptake inhibitor (SSRI) paroxetine can modulate vagal tone at the level of the mid-brain and inhibit the vasovagal reflex. Paroxysm of refractory neurally mediated syncope has been reduced with paroxetine. That finding supports the notion that paroxetine may modulate the occurrence of atrial fibrillation that is under the influence of the vagus nerve. In one study, oral paroxetine 10 mg/day was administered to nine patients with multidrug-resistant paroxysmal atrial fibrillation. Conventional antiarrhythmic drugs were used for all the patients for a minimum of 2 weeks, and, in the case of amiodarone, at least 3 months. These agents decreased the frequency of arrhythmia events by < 30% in all patients. In contrast, the frequency decreased significantly in all patients after paroxetine was added. Notably, in three patients, atrial fibrillation resolved completely. In three other patients, the daily doses of antiarrhythmic drugs were decreased by 33% to 50%, although the frequency of atrial fibrillation still remained low. For the group as a whole, the mean atrial fibrillation frequency declined from a baseline of 13.2 to 1.0 episodes per month. These preliminary results indicate that some patients with atrial fibrillation may respond very favorably to oral treatment with paroxetine. While the pathophysiology underlying this effect is not known, several possibilities exist, including modulation of central serotonin metabolism at the level of the mid-brain and anxiolysis resulting in decreased myocardial irritability. Whether the reputed benefit of paroxetine or other SSRIs in the treatment of atrial fibrillation depends upon the presence of comorbid depression is a question worthy of further study.

This column presents a case of treatment-resistant depression (TRD) in which the transdermal--but not the oral--formulation of selegiline was effective.