Bipolar Disorder: Silverstone P

Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP, Anonymous00076. · Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. · Bipolar Disord. · Pubmed #15952957 No free full text.

Abstract: Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

Ravindran A, Silverstone P, Lacroix D, van Schaick E, Vermeulen A, Alexander J. · Centre for Addiction and Mental Health, Toronto, Ontario, Canada. · Clin Pharmacokinet. · Pubmed #15301577 No free full text.

Abstract: OBJECTIVE: Divalproex sodium can interact with many drugs in which combination treatments are used; it can increase plasma concentrations of some drugs by inhibiting metabolism and can increase the free fractions of other medications by displacing them from plasma proteins. The combination of risperidone and divalproex sodium is used to treat the manic phase of bipolar disorder. However, the effect of risperidone on the pharmacokinetics of valproate has not previously been systematically studied. The aims of this study were to determine the effect of repeated doses of oral risperidone on the pharmacokinetics of valproate in subjects stabilised on divalproex sodium and to document the safety of this combination. STUDY DESIGN: A multicentre, observational, randomised, parallel group, single-blind, placebo-controlled drug interaction study. PATIENTS: Twenty-two patients with bipolar disorder, in remission, were studied. METHODS: All subjects were treated with divalproex sodium 1000 mg/day monotherapy on days 1-14. Thereafter, subjects continued to take divalproex sodium for days 15-28; they also received adjunctive treatment with either placebo (n = 11) or risperidone (n = 11) 2mg once daily on days 15 and 16, and 4 mg once daily on days 17-28. Serial blood sampling was performed throughout to determine the plasma concentrations of valproate, risperidone and 9-hydroxy-risperidone. RESULTS: On analysis, steady-state pharmacokinetic parameters (peak plasma concentrations [C(max)], time to C(max,) area under the concentration-time curve) of valproate were of the same order of magnitude on day 14 (monotherapy) and day 28 (valproate plus risperidone or placebo), with no period effect. The parameters on day 28 were similar in the risperidone and placebo treatment groups, showing that risperidone, as adjunctive treatment, had no influence on the steady-state pharmacokinetics of valproate. Although there were more adverse events reported in the risperidone group compared with the placebo group (ten vs seven, respectively), none of them were serious or necessitated withdrawal. No clinically relevant changes in laboratory parameters, vital signs or ECG-tracings were observed in either group. CONCLUSION: These results indicate that adjunctive risperidone treatment had no influence on the steady-state pharmacokinetics of valproate and this combination was safe and well tolerated.

Silverstone P. · Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada. · J Psychiatry Neurosci. · Pubmed #16151543 links to  free full text

This publication has no abstract.

Beck C, Silverstone P, Glor K, Dunn J. · Department of Psychology, University of Alberta, Edmonton. · Can J Psychiatry. · Pubmed #10500869 No free full text.

Abstract: OBJECTIVE: To survey Alberta psychiatrists on their prescribing of psychostimulants to adults. METHOD: A questionnaire was mailed to all 245 registered psychiatrists in Alberta. The respondents were requested to anonymously report, for the previous year, the number of adult patients to whom they prescribed pemoline, methylphenidate, amphetamines, or other psychostimulants for the treatment of adult attention-deficit hyperactivity disorder (ADHD), narcolepsy, unipolar depression, bipolar disorder, dementia, and other disorders. RESULTS: The response rate was 93.9%; 88.7% treated adults. Of these, 46.6% prescribed psychostimulants to 1238 patients. The greatest proportion of prescriptions of psychostimulants was for adult ADHD, depression, and narcolepsy. CONCLUSIONS: Psychostimulants are more widely prescribed by psychiatrists than indicated in earlier studies and in recommendations for treatment.