Faculty Bibliography

Reports a case in which a patient presents with persistent and refractory psychosis after treatment with interferon (IFN)-alpha . A 50-year-old white male was brought to the emergency room by a family member who had become concerned by his increasing paranoia and bizarre behavior. His psychiatric history was significant for a 25-year history of narcotic dependence, two brief admissions to substance-dependence treatment facilities, and a remote suicide attempt. The patient was treated with olanzapine and showed substantial, albeit incomplete, remission of his symptoms. However, shortly thereafter the patient became nonadherent with treatment and experienced a worsening psychosis that necessitated readmission. Olanzapine was increased to 25 mg/day. One more month of inpatient treatment resulted in a decrease in auditory hallucinations, but there was no reduction in the persecutory delusions.

Previous 'Psychopharmacology Reviews' columns have discussed the use of lamotrigine for bipolar disorder, refractory unipolar depression, treatment-resistant schizophrenia, posttraumatic stress disorder, frontal lobe dementia, and post-stroke pathological laughing and crying. Lamotrigine is an anticonvulsant that blocks voltage-gated sodium channels where it inhibits the excessive release of the excitatory amino acids glutamate and gamma -aminobutyric acid. In addition to its actions on ion channels, lamotrigine weakly inhibits monoamine transporters. At a concentration of 100-1,000 mM, lamotrigine is an inhibitor of 5-hydroxytryptamine uptake in both rat and human tissues. At similar concentrations, lamotrigine also inhibits norepinephrine and dopamine uptake into rat brain synaptosomes. Now comes a report of a woman with bipolar disorder who developed hair loss as a side effect of lamotrigine. (journal abstract)

Pica, defined as the ingestion of nonfood items, likely represents a form of obsessive-compulsive disorder (OCD). Predisposing factors include developmental disabilities, seizure disorders, depression, and OCD. Medication treatments for pica include selective serotonin reuptake inhibitors, tricyclic antidepressants, carbamazepine, and haloperidol. The following is a report on the successful use of the aminoketone norepinephrine and dopamine reuptake inhibitor, bupropion, for the treatment of chronic, persistent, severe nicotine-craving pica in a developmentally disabled adult. (journal abstract)

Rabbit syndrome is characterized by involuntary, rapid, fine, rhythmic vertical movements of the perioral muscles resembling the chewing movements of a rabbit. It usually occurs after long-term treatment with antipsychotics, including atypicals such as risperidone. Historically, rabbit syndrome has been reported with a variety of neuroleptic agents but not with other classes of psychotropic medications. Usually, patients with rabbit syndrome manifest other Parkinsonian signs such as rigidity, bradykinesia, or tremor. Methylphenidate is a psychostimulant agent that blocks catecholamine reuptake and directly stimulates the release of dopamine and norepinephrine. The following is the first published report of rabbit syndrome in association with the use of methylphenidate in an 8-year-old male with attention-deficit/hyperactivity disorder (ADHD). (journal abstract)

Baclofen, the Upsilon -aminobutyric acid (GABA)-sub(B) agonist muscle relaxant, has been commonly used to treat muscle spasms associated with various neurologic conditions including spinal injury, hemi-facial spasm, multiple sclerosis, trigeminal neuralgia, and neuroleptic-induced tardive dyskinesias. The usual dosage ranges from 10-200 mg/day. While baclofen is generally well tolerated, adverse effects are not uncommon, especially when higher doses are used. The following is a report of psychosis associated with use of therapeutic doses of baclofen.

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.