1998 APA Report, Part III

To ascertain a possible genetic component to tardive dyskinesia (TD), the relationship between presence or absence of TD and the dopamine(Drug information on dopamine) D3 receptor (DRD3) and the serotonin2A (5-HT2A) receptor gene was examined in 91 schizophrenic patients in a long-stay state hospital.

In this case-control design study, quantitative measures of TD were tested with ANOVA. This disclosed a positive association for orofacial movements and the DRD3 gene (p=0.004), and for abnormal movements in the extremities and the 5-HT font size="-2">2A gene (p=0.002). Interaction between the two polymorphisms seems to be of paramount importance on abnormal movements in both areas.

This data suggest that the occurrence of TD is probably highly related to a genetic predisposition whose effects become phenotypically evident with the significant contribution of other variables, especially neuroleptic treatment and aging (MacCiardi F et al., New Research 384).

To determine if estrogen replacement therapy (ERT) may augment antidepressant response to sertraline (Zoloft), 34 depressed female outpatients receiving sertraline and ERT were compared with 93 women who were receiving sertraline but not ERT. They were enrolled in either of two 12-week, randomized, double-blind, multicenter trials comparing sertraline (50 mg/day to 150 mg/day) with either fluoxetine(Drug information on fluoxetine) (Prozac) in one trial or nortriptyline(Drug information on nortriptyline) (Pamelor, Aventyl) in the other.

Based on Clinical Global Impression (CGI) scores, sertraline-treated women on ERT had substantially greater improvement than sertraline-treated women not taking ERT. There was a statistical trend for similar results on CGI mean change and on the proportion of women "remitting" (defined as HAM-D-17 scores =7).

These findings provide further evidence that ERT may augment clinical response to SSRI antidepressant treatment in older depressed women. ERT status of postmenopausal women should be considered during both treatment and the planning of clinical trials (Schneider LS et al., New Research 426).

To investigate if patients with obsessive-compulsive disorder (OCD) who relapse after drug discontinuation are responsive to drug reinstitution, a six-month, open-label reinstitution study was performed. A total of 81 outpatients who were responders (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score decrease >40%) to a prior trial (six months) with clomipramine(Drug information on clomipramine) 150 mg/day, fluoxetine 40 mg/day, fluvoxamine(Drug information on fluvoxamine) 300 mg/day or paroxetine(Drug information on paroxetine) (Paxil) 40 mg/day and who relapsed within six months of discontinuation, had the same treatment reinstituted (18 were retreated with clomipramine, 22 with fluoxetine, 21 with fluvoxamine and 20 with paroxetine). Each patient was scored on the Y-BOC Scale before entering the study and every two weeks until endpoint. Patients with at least 40% decrease of Y-BOCS score were rated as responders.

At endpoint, the response rate was 83.3% with clomipramine, 81.8% with fluoxetine, 80.9% with fluvoxamine and 80% with paroxetine-response rates considerably lower than the 100% rates of the first treatment with these drugs. Furthermore, Y-BOCS scores for the four groups showed a slower decrease after drug reinstitution than in the first trial.

Thus, relapsed OCD patients retreated with the same drug may respond to the same drug, but not as well or as quickly as the first time (Ravizza L et al., New Research 443).

During a six-month, double-blind, controlled, comparative clinical trial of olanzapine and risperidone(Drug information on risperidone) performed predominantly on patients with schizophrenia, serum prolactin was assessed at baseline, after completion of up to eight weeks acute treatment and after 28 weeks extended treatment.

After both treatment periods, mean prolactin for risperidone-treated males and females was significantly higher than that of olanzapine(Drug information on olanzapine)-treated males and females. Mean prolactin after acute and extended olanzapine treatment was not significantly different from baseline in either gender. Risperidone-treated females had a significantly greater increase in mean change from baseline prolactin than risperidone-treated males after both treatment periods. Mean change from baseline did not differ significantly between olanzapine-treated males and females.

These findings confirm that risperidone may cause an elevation in prolactin in men and women (females?males), whereas olanzapine is not associated with a significant increase in prolactin in either gender (Kinon B et al., New Research 449).

Researchers at George Washington University conducted a study to determine if olanzapine is a safe and effective add-on treatment for outpatients with mood disorders.

All charts of patients meeting DSM-IV criteria for bipolar disorder (n=7, type I, type II, NOS), unipolar major depressive disorder (n=1) or schizoaffective disorder (n=2, 1 bipolar type, 1 depressed type) treated with olanzapine in an outpatient psychiatric practice were reviewed. The CGI Scale for Improvement was used to retrospectively record clinical response.

Among the six males and four females (age 53.5?10.4 years), olanzapine (dose 8.75?8.68 mg/day for 15.1?16.8 weeks) was moderately effective in six (60%). The main indications for treatment were depressive (in six) or manic (in three) symptoms, with equal response in both groups (4/6 and 2/3, respectively). Only one patient possessed psychotic symptoms.

Eight patients reported side effects-most commonly weight gain (n=3); two of the 10 discontinued treatment due to side effects (weight gain, angioedema). Nine patients received mood stabilizers, and seven, antidepressants. Five patients had previously failed to respond to at least one mood stabilizer. Manic psychotic symptoms worsened in two patients-transiently in one case, and more severely in the other.

In conclusion, it appears from this study that olanzapine is an effective add-on treatment for outpatients with mood disorders. While side effects do occur, they usually do not lead to discontinuation (Ghaemi SN et al., New Research 57).

Efficacious treatment of BPD has been achieved with numerous medications, however, acceptability of older medications has been problematic. Researchers from Case Western University conducted a chart review of patients with BPD, most of whom have other comorbid illnesses. The patients were treated with atypical antipsychotics, such as risperidone, olanzapine and clozapine(Drug information on clozapine) (Clozaril). Twenty-five patient charts were reviewed. The adult patients, ranging in ages from 22 to 54, were 84% female and 84% Caucasian. Numerous medications had been used to treat all patients previously, with only minimal or partial response.

The design of the study included a chart review questionnaire that was systematically applied to the patients' records. The chart review was conducted not only by the clinicians but by other investigators as well. Data collected by the investigators led them to believe that the atypical antipsychotics administered were helpful in reducing a number of the symptoms characteristic of BPD. The CGI scores averaged 6.34 at the end of treatment with atypical antipsychotics. An average increase of 22.6% was observed in the Global Assessment of Functioning (GAF). The symptoms showing the greatest response included mood and affect, paranoia and fearfulness, suicidal thoughts, affective instability, sleep, controls and impulsivity. Additionally, the medications appeared safe and well-tolerated by the patients. These medications offer hope for the future treatment of patients suffering from BPD (Kujawa MJ et al., New Research 84).

Corticosteroids are medications that are frequently prescribed for a variety of common illnesses. However, corticosteroid therapy has been known to produce side effects that include mania, depression, mood lability and psychosis. Researchers in the department of psychiatry at the University of Texas, Southwestern, reported preliminary data from an investigation in which they hope to help resolve the ongoing problem of poorly characterized symptoms and risk factors.

The investigation targeted asthma-suffering outpatients (n=23) receiving prednisone(Drug information on prednisone) (Sterapred) therapy (generally 40 mg/day for one to two weeks). Psychiatric symptoms were characterized using a structured clinical interview, HAM-D, Young Mania Rating Scale (YMRS), BPRS and Internal State Scale (ISS). These data show significant increases in the YMRS (p=0.003) after four to seven days of corticosteroid therapy.

Persons with a history of major depressive disorder showed significantly increased scores on the Well-Being Subscale of the ISS (p=0.04) and a trend towards decreased HAM-D scores (p=0.08) compared with persons without a history of depression.

It has been reported that persons experiencing posttraumatic stress disorder (n=5) sometimes report a worsening of symptoms and depression during prednisone therapy, although this data was not statistically significant. Therefore, these preliminary data suggest that symptoms of hypomania are common with corticosteroids and that psychiatric history may help predict response (Brown ES et al., New Research 99).