Ronald Brenner

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.

Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation A Randomized, Controlled Trial

OBJECTIVE Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimers Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia. METHODS This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability. RESULTS Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences. CONCLUSIONS This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.

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.

Pharmacological treatment of the psychosis of Alzheimer's disease: what is the best approach?

Psychosis of Alzheimer’s disease (PAD) forms part of the behavioural and psychological symptoms of dementia (BPSD). PAD includes symptoms of psychosis such as hallucinations or delusions, and may be associated with agitation, negative symptoms or depression. Even though the US FDA has not approved any medication for the treatment of PAD, atypical antipsychotics have been widely used and favoured by geriatric experts in the management of the condition in view of their modest efficacy and relative safety. However, the recent FDA warnings regarding the cardiac, metabolic, cerebrovascular and mortality risks associated with the use of these drugs in elderly patients with dementia have caused serious concerns regarding their use. Nevertheless, until an effective and safe medication is approved by the regulatory agencies for PAD, clinicians do not have a better choice than atypical antipsychotics for the management of the serious symptoms of this condition.

Role of Atypical Antipsychotics in the Treatment of Psychosis and Agitation Associated with Dementia

The drug treatment of elderly patients is challenging because of the various pharmacokinetic and pharmacodynamic changes associated with increasing age, and the frequent comorbid medical conditions found in and multiple concurrent medications used by this population.Behavioural symptoms, such as agitation and psychosis, commonly occur with dementia. Until recently, conventional antipsychotics were the mainstay of treatment, but their use in geriatric patients is limited because of serious adverse events. Compared with conventional antipsychotic agents, risperidone, olanzapine and quetiapine appear to be generally well tolerated in the elderly population (the use of clozapine is limited by its adverse effects). However, only 1 large controlled trial of one of these atypical antipsychotics (risperidone) in the treatment of behavioural symptoms of dementia has been published. While data indicate that risperidone may be the drug of choice, head-to-head, double-blind, controlled, comparative studies assessing the efficacy, tolerability and pharmacoeconomics of atypical antipsychotics in patients exhibiting behavioural symptoms associated with dementia are warranted to clarify the most appropriate choice of treatment.

Brain Tumor and Psychiatric Manifestations: A Case Report and Brief Review

Brain tumors may present multiple psychiatric symptoms such as depression, personality change, abulia, auditory and visual hallucinations, mania, panic attacks, or amnesia. A case of a 79-year-old woman who presented with depressive symptoms but showed minimal neurological signs and symptoms is discussed. Neuroimaging revealed a brain tumor in the left parietal lobe, and patient underwent neurosurgical treatment and subsequently received chemotherapy and radiation. Some patients with neurologically silent brain tumors may present with psychiatric symptoms only. Therefore, we emphasize the consideration of neuroimaging in patients with a change in mental status regardless of a lack of neurological symptoms.

Use of Olanzapine for Elderly Patients with Psychotic Disorders: A Review

The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.