Faculty Bibliography

While the exact pathophysiology of tinnitus remains unknown, possible causes include cochlear deterioration; an extra-auditory response to respiratory, vascular, or muscular stimuli; a drug reaction; microvascular compression of the eighth cranial nerve; and turbulent flow in the ipsilateral internal carotid artery. Regardless of the cause, tinnitus may result in significant diminution of quality of life. Proposed treatments include retraining therapy, maskers, hyperbaric oxygen, carotid artery stenting, selective cochlear neurotomy, and biofeedback, as well as pharmacotherapy with antidepressants, benzodiazepines, lidocaine, the calcium channel blocker nimodipine, or botulinum toxin. The double-blind, placebo-demonstrates the effectiveness of the selective serotonin reuptake inhibitor (SSRI) sertraline for the treatment of severe tinnitus. The findings support a possible role for sertraline, and likely other SSRIs, for the treatment of refractory tinnitus.

The following is a report of Pisa syndrome in association with the gamma -aminobutyric acid-ergic anticonvulsant and mood-stablizer medication, sodium valproate. A 65-year-old nursing home resident with schizoaffective disorder used a wheelchair due to severe arthritis. His medications included valproic acid 750 mg BID, carbamazepine 200 mg BID, and risperidone 3 mg BID, a regimen that had been stable and remained unchanged over several months. Routinely monitored, his valproic acid and carbamazepine levels never exceeded the therapeutic range. Over the course of several weeks, the nursing home staff noticed that the patient had begun leaning to one side. The only medication change to which the patient consented was a trial discontinuation of valproic acid, which resulted in immediate resumption of his posture to a stable, upright position. The finding of Pisa syndrome resolution after valproic acid discontinuation suggests that this anticonvulsant was involved in the pathogenesis of this reaction, either individually or through a pharmacodynamic interaction with another drug, most likely risperidone.

Priapism, characterized by abnormal, prolonged, painful erection of the penis, is a urologic emergency. If not treated within 4-6 hours, complications may occur, including difficulty urinating, urinary retention, impotence, cavernosa fibrosis, and gangrene. Even with surgery, approximately 40% to 50% of patients with priapism will become impotent. Priapism results from decreased venous outflow from the corpora cavernosa. This can be caused by physical obstruction of the venous system, blood dyscrasias that impede venous flow, solid tumors, trauma, spinal cord injuries, stroke, or blockade of postsynaptic alpha 1-adrenergic receptors that normally mediate sympathetically controlled detumescence of the penis or clitoris. In general, drug-induced priapism is believed to be mediated by the degree of aradrenergic antagonism. Opposing this tendency are anticholinergic effects. Thus, when a medication has more antiadrenergic than anticholinergic properties, it is more likely to be associated with priapism. Based on a review of available evidence, medication-induced priapism does not appear to correlate with either dose or length of treatment.

The following is a report of galantamine-induced QTc interval prolongation. A 47-year-old white male with chronic schizophrenia, diabetes, hypertension, and hyperlipidemia presented in 2004 on a psychotropic drug regimen of aripiprazole, quetiapine, lithium, benztropine and trazodone as needed for sleep. Other medications included aspirin, docusate, enalapril, insulin, lactulose, metoprolol, ranitidine, simvastatin, and vitamin E. After obtaining written informed consent, the patient was started on galantamine 4 mg BID. Immediately prior to initiation of galanfamine, his QTc was 417 msec and his heart rate was 71 beats/minute. In the 5 years prior to his starting on galantamine, on his annual electrocardiogram (EGG), his QTc interval had ranged from 420-443 msec. An EGG obtained 3 months prior to initiation of galantamine revealed a QTc of 415 msec. During the trial of galantamine, the doses of his other medications were held constant. One month after galantamine initiation, his serum lithium level was 0.44 mEq/L. Over a 2 month period, galantamine was titrated to 12 mg BID, at which time an EGG demonstrated a QTc of 518 msec. Galantamine was immediately discontinued, and over the next 1-2 weeks, the QTc shortened to 459 msec and to 414 msec, respectively. This case represents the first published report of QTc prolongation in association with galantamine.

Quetiapine fumarate is an atypical neuroleptic indicated for the treatment of schizophrenia. It is also used as both a monotherapy for the acute treatment of manic episodes and as an adjunct to treatment with lithium or divalproex associated with bipolar type 1 disorder. Pharmacologically, it is an antagonist at serotonin (5-HT)1A and 5-HT2, dopamine (D)1 and D2, histamine H1 and adrenergic alpha 1 and alpha 2 receptors. According to the package insert, in clinical trials of the drug there were small dose-related decreases in thyroid hormone, particularly total T4 and free T4; however, only 0.4% of subjects studied experienced significant increases in thyroid stimulating hormone (TSH) levels. In previously reported cases of quetiapine-induced hypothyroidism, most of the patients either had a history of compromised thyroid function or had normal TSH levels. In addition, no anti-thyroid antibody titers were measured in these studies. The following is a report of a depressed patient treated with quetiapine who developed hypothyroidism that remitted after drug discontinuation.

Wagstaff et al (2003) have summarized case reports of statin-induced memory problems in patients treated with simvastatin. This article presents a report of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy. A 64-year-old white male presented with memory problems shortly after initiation of simvastatin therapy. The man had a history of bipolar disorder, characterized predominantly by depressive episodes, which had been stable over the past 2 years. At the time of presentation, the patient's medications included venlafaxine, quetiapine fumarate, simvastatin, terazosin, and carbamazepine extended-release. Simvastatin had been initiated by the patient's primary care physician for dyslipidemia. Within 1 week of starting simvastatin, the patient complained of additional memory problems. The temporal sequence of events supports a highly probable association between simvastatin and cognitive decline in this patient.