International Psychopharmacology Research

April 15, 2004

A longitudinal study of the nicotine patch for smoking abstinence and a look at new drugs to lower blood pressure in patients with cerebrovascular disease are among the various research studies from Europe, Australia and Asia highlighted in this column.

Behavioral therapy and selective serotonin reuptake inhibitors have both been reported effective in the treatment of trichotillomania. Dutch researchers examined the efficacy of behavioral therapy and fluoxetine (Prozac) 60 mg/day compared with a waiting-list control group. Forty-three patients with trichotillomania participated in this 12-week, randomized, controlled study. Forty patients (behavioral therapy, 14; fluoxetine, 11; wait list, 15) completed the trial.

Treatment effects were evaluated using the Massachusetts General Hospital Hairpulling Scale. Severity of hair loss was rated by independent assessors. General symptoms of psychopathologic abnormalities and depression were also measured.

Behavioral therapy was found to be superior for reducing the symptoms of trichotillomania. Patients in the behavioral therapy group had significantly reduced trichotillomania symptoms, higher effect sizes (behavioral therapy, 3.80; fluoxetine, 0.42; wait list, 1.09), and more clinically significant changes than patients in the fluoxetine and wait-list groups (behavioral therapy, 64%; fluoxetine, 9%; wait list, 20%). A similar trend was also found for severity of hair loss. No significant differences between groups were established for general psychopathologic and depressive symptoms.

The researchers concluded, "Behavioral therapy is highly effective for reducing symptoms of trichotillomania in the short term, whereas fluoxetine is not."

Reference: van Minnen A, Hoogduin KA, Keijsers GP et al. (2003), Treatment of trichotillomania with behavioral therapy or fluoxetine: a randomized, waiting-list controlled study. Arch Gen Psychiatry 60(5):517-522.

Low Nevirapine Plasma Concentrations Predict Virological Failure in an Unselected HIV-1-Infected Population

De Vries and colleagues (2003) reported on the results of a study assessing plasma nevirapine (Viramune) concentrations and plasma HIV-1 RNA response in patients infected with HIV-1.

Plasma samples were obtained from 189 patients receiving nevirapine 200 mg twice daily. Plasma nevirapine concentrations were measured with reverse phase high performance liquid chromatography. Patients were divided into two groups based on plasma nevirapine concentrations of either ≤ 3 mg/L or >3 mg/L. Multivariate analysis determined the association between steady-state nevirapine concentrations and plasma HIV-1 RNA.

Thirteen patients had low plasma concentrations of nevirapine, and 176 patients had concentrations >3 mg/L. In total, 22 (12%) patients had virological failure, and eight patients (4%) discontinued nevirapine due to adverse effects. There was an increased risk of failure in patients with nevirapine plasma concentrations ≤ 3 mg/L (relative risk=5.0, 95% confidence interval [CI]: 1.8-13.7). Eight percent of the patients experienced rashes and liver enzyme elevations. The researchers concluded, "Low nevirapine drug concentrations are predictive of virological failure."

Reference: deVries-Sluijs TE, Dieleman JP, Arts D et al. (2003), Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population. Clin Pharmacokinet 42(6):599-605.

Abstinence From Smoking Eight Years After Participation in Randomised Controlled Trial of Nicotine Patch

Researchers in the United Kingdom reported the results of a study investigating abstinence from smoking in an eight-year follow-up of participants in a randomized controlled trial of the nicotine patch.

Eight-hundred forty participants completed a questionnaire providing demographic details and information about smoking. The eight-year abstinence rate was 5%, and the relapse rate was 46%.

Reference: Yudkin P, Hey K, Roberts S et al. (2003), Abstinence from smoking eight years after participation in randomised controlled trial of nicotine patch. BMJ 327(7405):28-29.

Effects of Blood Pressure Lowering With Perindopril and Indapamide Therapy on Dementia and Cognitive Decline in Patients With Cerebrovascular Disease

Because high blood pressure and stroke are associated with increased risks of dementia and cognitive impairment, Australian investigators published a report on the results of a study to determine whether lowering blood pressure would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease.

This study was a randomized, double-blind, placebo-controlled trial conducted among 6,105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (n=3,051) or matching placebos (n=3,054). Perindopril (Aceon) was given to all participants, and indapamide (Lozol) was given to those with neither an indication for nor a contraindication to a diuretic.

The primary outcomes for these analyses were dementia, (using DSM-IV criteria) and cognitive decline (a decline of ≥3 points on the Mini-Mental State Exam [MMSE] score). The results were from a mean follow-up of 3.9 years.

Dementia was documented in 193 (6.3%) of the actively treated group and 217 (7.1%) of the placebo group (relative risk reduction=12% [95% CI: -8% to 28%]; p=0.2). In the active treatment group, 9.1% of patients had a cognitive decline, as did 11% of the placebo group (risk reduction=19% [95% CI: 4% to 32%]; p=0.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% CI: 3% to 55%; p=0.03) and 45% (95% CI: 21% to 61%; p<0.001), respectively. There was no clear effect on either dementia or cognitive decline in the absence of recurrent stroke.

These findings, the authors concluded, indicated:

Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.

Reference: Tzourio C, Anderson C, Chapman N et al. (2003), Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 163(9):1069-1075.

Occurrence of Spontaneous Dyskinesia in Chronically Ill Never-Treated Schizophrenic Patients: An Update

In Southern India, a group of researchers had found that spontaneous dyskinesia is common in chronically ill patients who had never been treated for schizophrenia. More recently, they reported that they have found brain structure changes in these patients via magnetic resonance imaging. In contrast to patients without dyskinesia, the left lenticular nucleus is larger in patients with dyskinesia and, compared with controls, the right lateral ventricle to hemisphere ratio is larger in patients without dyskinesia. Furthermore, in controls, increasing age was associated with decreased basal ganglia volume. These findings indicate there is a subgroup of patients with schizophrenia and dyskinesia striatal pathology.

Reference: McCreadie RG, Thara R, Padmavati R et al. (2002), Structural brain differences between never-treated patients with schizophrenia, with and without dyskinesia, and normal control subjects: a magnetic resonance imaging study. Arch Gen Psychiatry 59(4):332-336.