Therapeutic Advances in Psychopharmacology

Patients prescribed clozapine were surveyed to assess (a) the effects, both positive and adverse, and overall satisfaction with clozapine in comparison to previously prescribed antipsychotics and (b) the relative significance of effects experienced, both positive and adverse, in terms of impact on subjective well-being.

A total of 56 male patients prescribed clozapine at a forensic psychiatric hospital were surveyed using a 27-item questionnaire. All patients had been prescribed clozapine for a minimum of 3 months. Respondents were asked to rate effects and satisfaction with clozapine treatment in comparison with previously prescribed antipsychotic medication on a five-point scale. Respondents were also asked to rate effects experienced with clozapine treatment in terms of impact on subjective well-being on a five-point scale.

A total of 89% of respondents reported greater satisfaction with clozapine than with previously prescribed antipsychotic medication. A majority of patients reported positive effects in terms of an improvement in their quality of life (68%) and social abilities (52%) with clozapine in comparison with previously prescribed antipsychotics. Nocturnal hypersalivation (84%) and weight gain (57%) were the most common adverse effects. Hedonic responses were assessed for each effect in order to determine the associated subjective experiences. The most positive hedonic responses were for quality of life, mood and alertness. In terms of adverse impact on subjective well-being, nocturnal hypersalivation ranked highest.

Patients in a UK forensic sample are largely satisfied with clozapine treatment. The subjective effects of clozapine treatment should be taken into account by clinicians when assessing response. This may provide an opportunity to highlight the positive changes and prioritize management of the most undesirable adverse effects, which is likely to promote compliance and improve longer term treatment outcomes.

This study examined 5-year outcomes of patients prescribed risperidone long-acting injection (RLAI) or aripiprazole in a clinical setting, using treatment discontinuation as a measure of effectiveness.

Patients who received RLAI or aripiprazole in the 18 months following their respective UK launches were included. Two-year outcome data were previously reported for these cohorts; this study reported an additional 3 years of follow up for each group. Data were collected from pharmacy records and by retrospective case note review. Patients were classified as continuers or discontinuers at 5 years and reasons for treatment discontinuation noted.

The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0).

There was no significant difference between the proportions of patients continuing RLAI or aripiprazole for 5 years. Continuation rates were relatively low (18% and 16% of the original RLAI and aripiprazole cohorts respectively), whilst coprescription of other antipsychotics at endpoint was relatively common. Lack of effectiveness was the most common reason for discontinuation of both compounds. These findings suggested that clinical effectiveness was somewhat disappointing, although the long period of follow up and number of patients previously treated with clozapine in the original cohorts were confounding factors.

Weight gain as an adverse effect of monotherapy of antidepressant has been well-studied. The effects of augmentation therapy involving multiple antidepressants, on weight changes needs to be adequately addressed.

To study the co-medication effects of bupropion in combination with six individual antidepressants on body mass index (BMI) using EMR based data analysis.

Allscripts data warehouse was used to identify patients on monotherapy of five selective serotonin reuptake inhibitor (SSRI) drugs, escitalopram, sertraline, citalopram, paroxetine, fluoxetine, one selective norepinephrine reuptake inhibitor (SNRI) duloxetine and the aminoketone, bupropion for at least 180 days. We also identified patients on co-medication of SSRI/SNRI drugs with bupropion. Six ANCOVA models were built to compare the short term effects on BMI, among monotherapy and co-medication groups. The patients’ clinical conditions and demographics were included to account for confounding effects.

Monotherapy of all the SSRI/SNRI drugs showed significant weight increase, consistent with that of previous studies. The co-medication of bupropion and escitalopram showed a significantly higher increase in BMI than monotherapy (P = 0.0102). The increase in BMI in the other five co-medication groups was not significantly different from their respective monotherapy groups.

Our study reports an adverse weight gain on co-medication of escitalopram and bupropion, which warrants further validation studies. Considering co-medication effects of antidepressants on weight is important to design robust depression treatment plans.

Current evidence supports the use of various second-generation antipsychotics for pharmacotherapy of schizophrenia. While in a systematic review, generally no difference in efficacy was found between atypical antipsychotics, other studies have found quetiapine less effective than aripiprazole. This article reviews the efficacy and tolerability of aripiprazole versus quetiapine in the context of recommended management strategies for schizophrenia.

Fifty female inpatients, meeting the diagnosis of schizophrenia, were randomly entered into two groups (n = 25 in each group) to participate in a 12-week, double-blind study for random assignment to quetiapine or aripiprazole. The primary outcome measures were Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms. The schedule for Assessment of Insight (SAI), Clinical Global Impressions Severity Scale (CGI-S) and the Simpson Angus Scale (SAS) were also used as secondary measures.

Both quetiapine and aripiprazole showed significant effectiveness in the improvement of positive symptoms. The effectiveness for negative symptoms was also noteworthy with both drugs, although not to a significant level during this study. In addition, significant improvement was found on assessment with CGI-S and SAI for quetiapine and aripiprazole. SAS did not show any important increment in extrapyramidal side effects at the end of the examination.

According to the findings, quetiapine and aripiprazole had similar effectiveness and tolerability with respect to management of schizophrenia.

Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

A literature review of the evidence supporting this hypothesis was performed.

The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.