Subramoniam Madhusoodanan

Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: A double-blind, randomized pilot study

BACKGROUND Hypericum (St. Johns wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE This study compared hypericum and the SSRI sertraline in the treatment of depression. METHODS In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks. RESULTS The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size. CONCLUSION The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.

Safety of benzodiazepines in the geriatric population

Benzodiazepines are the most frequently prescribed antianxiety drugs in the elderly. Despite their usefulness and safety in the younger population, there is concern about the rationale for their use in the elderly. Studies of the therapeutic use of benzodiazepines in the elderly are rare. Elderly females with co-morbid medical and psychiatric conditions and who are taking multiple medications form the group most frequently prescribed benzodiazepines among the elderly, and the group most likely to experience side effects. Age-related pharmacokinetic and pharmacodynamic changes increase the potential for certain side effects in the elderly. Significant adverse effects that may be associated with benzodiazepine use in the elderly include falls, cognitive impairment, sedation, and impairment of driving skills, all of which are particularly related to the long half-life of benzodiazepines. Long-term use of benzodiazepines should be discouraged because of the risk of dependence, which is a serious problem in the elderly. Unrecognised and untreated benzodiazepine dependence can lead to serious medical complications.

Hyperprolactinemia associated with psychotropics--a review.

Different classes of psychotropics can cause hyperprolactinemia to varying degrees. Among antipsychotics, typical agents and risperidone are the most frequent and significant offenders. In this review we discuss the pathophysiology, offending medications, assessment and management of hyperprolactinemia.

International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia.

OBJECTIVE The authors compared the effects of the two most commonly used atypical antipsychotics, risperidone and olanzapine, in elderly patients with schizophrenia. METHODS In an 8-week, international, double-blind study, patients (outpatients, hospital inpatients, and residents of nursing or boarding homes) were randomly assigned to receive risperidone (1 mg to 3 mg/day) or olanzapine (5 mg to 20 mg/day). The main outcome measures were changes in Positive and Negative Syndrome Scale (PANSS) total scores and rates of extrapyramidal symptoms (EPS). RESULTS Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder. The mean duration of illness was 36.5 years. Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine. PANSS total scores and four of the five PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, and anxiety/depression) improved significantly at all time-points and at endpoint in both groups; between-treatment differences were not significant. EPS-related adverse events were reported by 9.2% of patients in the risperidone group and 15.9% in the olanzapine group; the between-treatment difference was not significant. Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint; between-treatment differences were not significant. Clinically relevant weight gain was seen in both groups, but was significantly less frequent in risperidone patients than in olanzapine patients. CONCLUSIONS Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms, with a relatively low risk of side effects.

Experience with the atypical antipsychotics--risperidone and olanzapine in the elderly.

There is paucity of published data regarding controlled trials with risperidone and olanzapine in elderly psychotic patients. Medical records of 151 hospitalized geropsychiatric patients (risperidone patients n = 114 and olanzapine patients n = 37) were analyzed for demographic data, target symptoms, doses, effects, side effects, comorbid medical conditions and concurrent medications. The mean age of the patients was 71 years. The male: female ratio was essentially the same for both groups. The mean daily dose was 3 mg for risperidone and 10 mg for olanzapine. 78% of the risperidone group and 75% of the olanzapine group appear to have responded to treatment. The discontinuation rates of medication was the same in both groups (22%). Adverse events were reported in 16–17% in both groups. It appears from this study that both risperidone and olanzapine are relatively safe and effective in geropsychiatric patients with comorbid medical illnesses. Controlled studies and head-to-head comparison studies are recommended.

Managing bipolar disorder in the elderly: Defining the role of the newer agents

Clinical research in geriatric psychopharmacology has been a relatively neglected focus compared with the wealth of information on younger populations, and there is a dearth of published, controlled trials. Similarly, these are limited data in the area of geriatric bipolar disorder.Although there is an absence of rigorous, evidence-based information, preliminary data on older adults with bipolar disorder suggest some promising treatment options and important differences in older versus younger patients with bipolar illness. Lithium, while widely utilised in younger populations, is often poorly tolerated in the elderly. Clinical evidence regarding use of antiepileptic compounds in late-life bipolar disorder is generally compiled from bipolar disorder studies in mixed populations, studies in older adults with seizure disorders, and studies on dementia and psychotic conditions other than bipolar disorder. Valproate semisodium and carbamazepine are widely prescribed compounds in older adults with bipolar disorder. However, the popularity of these compounds has occurred in context of an absence of evidence-based data.The atypical antipsychotics have expanded the treatment armamentarium for bipolar disorder in mixed populations and may offer particular promise in management of bipolar illness in older populations as well. Olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole are atypical antipsychotics that have been approved by the US FDA for the treatment of bipolar disorder; however, there are no published, controlled trials with atypical antipsychotics specific to mania in geriatric patients. Preliminary reports on the use of clozapine, risperidone, olanzapine and quetiapine suggest a role for the use of these agents in late-life bipolar disorder. Information with ziprasidone and aripiprazole specific to geriatric bipolar disorder is still lacking.

Hyponatraemia Associated with Psychotropic Medications A Review of the Literature and Spontaneous Reports

Psychotropic medication-induced hyponatraemia is an uncommon but important clinical problem with potential serious consequences if not recognised and treated early. Several risk factors have been associated with the development of hyponatraemia. This article reviews reported cases of hyponatraemia associated with the use of psychotropic medications and evaluates possible risk factors and causes.The data were sourced by a search of Medline for reports of hyponatraemia associated with the use of psychotropic medication between January 1966 and December 2000 and a search of US Food and Drug Administration (FDA) spontaneous reporting system database between January 1966 and December 1999. All the reports were included in this review.In the case reports the following data were assessed: age, gender, daily dosage, days to onset, days to recovery, medical condition, concurrent medications. Several risk factors were identified: advanced age, female gender, use of other medications, medical comorbidity. The risk of hyponatraemia was found to be higher during the first 2 weeks of treatment. Administration of the dosage of the drug was not found to be related to the development of hyponatraemia. Hyponatraemia can cause confusion, agitation and lethargy. Any change in the course of illness should alert the physician to the possibility of hyponatraemia.

Clinical Experience with Quetiapine in Elderly Patients with Psychotic Disorders

Quetiapine fumarate is a recently marketed atypical antipsychotic medication proved to be effective in the treatment of schizophrenia and schizoaffective disorder in the younger population. There is a paucity of studies of this drug in the elderly and more data are needed on the effects of quetiapine in this population, especially those with comorbid medical illnesses. Quetiapine was used to treat seven elderly hospitalized patients between 61 and 72 years of age who manifested signs of psychosis related to schizophrenia, schizoaffective disorder, or bipolar disorder. All patients had been treated previously with conventional antipsychotics or other atypical antipsychotics. Response was assessed by observation of patients behavior. Four patients responded to treatment; three did not respond. Positive symptoms decreased markedly in all four responders. Negative symptoms showed marked decrease in two patients and moderate decrease in one patient. Preexisting extrapyramidal symptoms (EPS) diminished in three patients. Transient hypotension, dizziness, and somnolence occurred in two patients. No other side effects were noted. No adverse consequences occurred when lithium, carbamazepine, valproic acid, or venlafaxine was given concurrently. The reduction of positive and negative symptoms of schizophrenia and lack of significant EPS and minimal sedative, hypotensive, and anticholinergic side effects indicate that quetiapine may be a safe and effective medication for the elderly. (J Geriatr Psychiatry Neurol 2000; 13:28-32).

Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study.

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60–85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5–20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

The effect of anxiety and depression on completion/withdrawal status in patients admitted to substance abuse detoxification program.

A large proportion of patients entering substance abuse treatment carry psychiatric diagnoses, and some studies have found that those with psychopathology are more likely to withdraw before treatment is completed. We performed a prospective study of patients entering an inpatient substance abuse detoxification program to determine if the degree of anxiety and/or depression correlated with higher dropout rates. On entry to the unit, all patients were administered the Hamilton Rating Scales for Depression and Anxiety. Of the 148 patients studied, 97 (65.5%) completed treatment and 51 (34.5%) withdrew prematurely. There were no significant differences in Hamilton Depression and Anxiety Rating Scale scores between completers and withdrawers. This was true for the total study population, as well as for subgroups of patients based on primary drug abused (heroin or cocaine). Although anxiety and depression are common in substance abusers, we were unable to detect differences on validated anxiety and depression rating scales between those completing and those withdrawing from substance abuse detoxification.