Comparison of Combination Olanzapine+Lithium or Chlorpromazine+Lithium in Treatment of First Manic Episode With Psychotic Features

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by Melbourne Health.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Melbourne Health
ClinicalTrials.gov Identifier:
NCT00202293
First received: September 14, 2005
Last updated: NA
Last verified: September 2005
History: No changes posted
  Purpose

Aim: In a population of first episode manic patients with psychotic features, we want to compare the side effect profile, the degree of adherence and the subjective well being, as well as the efficacy of two treatments: The standard treatment currently applied (lithium + chlorpromazine) and an alternative treatment more recently introduced (lithium + olanzapine). In addition, we want to study retrospectively the development of bipolar disorder and study prospectively the 6 and 12-month outcome of a cohort of patients presenting a first manic episode with psychotic features.

Research Background: While the efficacy of lithium in the treatment of acute mania has been established by numerous studies, it is also known that up to 50% of the patients fail to respond when it is prescribed alone. It is therefore common practice to complement the treatment, most commonly with antipsychotics and benzodiazepines. It has been suggested that antipsychotic agents are faster acting and are superior in controlling hyperactivity compared to lithium, whereas mood stabilisation is better achieved by lithium, Typical antipsychotics, such as chlorpromazine, may therefore be useful as adjunctive medication to mood stabilisers, especially within the first few weeks of treatment of acute mania, and for patients exhibiting psychotic symptoms or hyperactivity. They however can induce side effects (somnolence, dizziness, dry mouth, extrapyramidal side effects such as rigidity of the muscles, and possibly tardive dyskinesia (involuntary movements or contraction of muscles), as well as akathysia (sense of restlessness). They finally have been suspected to contribute to the occurrence of post-manic depression. Recent publications in chronic populations have shown that atypical antipsychotics, such as olanzapine, are also an effective adjunctive treatment. Olanzapine has the important advantage to induce a very low incidence of extrapyramidal side effects, including tardive dyskinesia. It can however induce somnolence, dizziness, dry mouth, and rather commonly weight gain. Moreover, some authors have reported that olanzapine might induce mania. Both treatments appear then to have positive effects as well as undesirable side effects. Our project is to compare them. The literature concerning first episode mania is sparse, particularly in the domain of pharmacotherapy. One retrospective study showed that 77% of the patients received antipsychotics at discharge and 25% at 6 months follow-up. No comparison has however been made between typical and atypical antipsychotics, and there are no specific treatment guidelines of first episode mania with psychotic features.

Project Summary: The hypothesis is that olanzapine and chlorpromazine will have a comparable efficacy as adjunctive treatment of the acute manic episode with psychotic features. We however think olanzapine will induce less side effects and will be better accepted by the patients, and therefore that the adherence to the treatment will be better than with chlorpromazine. We finally think the subjective sense of well being will be greater with olanzapine than with chlorpromazine.We will recruit 75 patients at the time of their first admission for mania with psychotic features at EPPIC. After signature of the informed consent, we will perform a baseline assessment first to confirm the diagnosis, and second to evaluate the level of psychopathology. The patients will then be randomly selected to receive either a treatment of lithium and olanzapine or a treatment of lithium and chlorpromazine. By the end of the study there will be 37 patients in each group.The patients will go through a baseline assessment including physical examination and usual laboratory investigation to exclude any physical illness. They will also go through a one-hour assessment of psychopathology. Between day 2 and 3 they will go through 2 hours of interview to reassess diagnosis and personal history. They will thereafter be assessed weekly for eight weeks on various dimensions: evolution of the intensity of the symptoms, appearance of depressive symptoms, occurrence of side effects and degree of adherence to the treatment, in an 1-hour interview. Subjective well being and quality of life will re evaluated at week 4 and 8, adding 45 minutes to the duration of the interview. This is a flexible dose, open trial, which means the doctor in charge of the patient will know which medication is being prescribed, and that he will be allowed to adapt the dosage according to what he feels necessary. This research project will allow us to organise a more specialised clinic for the care of first episode manic patients. We will take this opportunity to study carefully the months preceding the appearance of the first episode in order to try to reconstruct the prodrome of bipolar disorders. We will also, in an extension phase of the study, look at the long term outcome (at 6 and 12 months) of a first episode of mania.


Condition Intervention Phase
Bipolar Disorder
Schizoaffective Disorder
Drug: Olanzapine
Drug: Lithium
Drug: Chlorpromazine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: Comparison of Combination Olanzapine and Lithium and Combination Chlorpromazine and Lithium in the Treatment of a First Manic Episode With Psychotic Features.

Resource links provided by NLM:


Further study details as provided by Melbourne Health:

Primary Outcome Measures:
  • Safety
  • ¨The frequency of treatment-emergent adverse events (events that first appear or worsen during the study period) will be compared between both groups.
  • ¨The frequency of side effects as rated with the UKU scale will be compared between both groups.
  • ¨Weight gain will be compared between both groups.
  • ¨Frequency of changes in vital signs and laboratory findings will be compared between both groups.
  • Subjective well being
  • ¨Total scores on the DAI and the SWN will be compared between both groups.

Secondary Outcome Measures:
  • Adherence
  • ¨Degree of adherence to the treatment as scored on the MARS will be compared between both groups.
  • Efficacy
  • ¨End point analysis: Mean change in various scales from baseline to week 4 and week 8 will be used to compare the efficacy of the two treatments:
  • ¨Primary efficacy analysis will be assessed by comparing the mean change in theYMRS total score.
  • ¨Secondary efficacy analysis will be assessed by comparing the mean change in CGI-BP total score and in BPRS total score.
  • ¨Response analysis: Response is defined as at least a 50% drop in the total YMRS total score from base line to the 8-weeks end point. Euthymia is defined as a total score on the YMRS of no greater than 12 at end point. The number of patients reaching bot
  • Incidence of depressive episodes
  • ¨A worsening in the HAMD-21 score of at least 3 points will be used as a definition of a clinically detectable worsening in depressive symptoms.
  • Six and 12 months outcome
  • Definition of recovery:
  • ¨Syndromic recovery: Eight contiguous weeks [50] during which the patient no longer meets criteria for a manic, mixed, or depressive syndrome. Recovery from each of these syndromes is based on DSM-IV criteria and is operationalised as follows: manic synd
  • ¨Symptomatic recovery: Eight contiguous weeks [50] during which the patient experiences minimal to no psychiatric symptoms, operationalized as follows: Young Mania Rating Scale total score of 5 or less, Hamilton depression scale total score of 10 or les
  • ¨Relapse: Relapse is defined as the return of symptoms after a remission of less than 8 weeks.
  • ¨Recurrence: Recurrence is defined as return of symptoms after recovery.
  • ¨Functional recovery: Return to premorbid levels of function for at least 8 contiguous weeks [50]. To assess functional recovery, seven of the nine general items from the Premorbid Adjustment Scale are evaluated at the 6 and 12-month follow-up visit for

Estimated Enrollment: 75
Study Start Date: October 2001
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients aged 15 to 29.
  • Experiencing a first episode psychosis.
  • Meet DSM-IV criteria for bipolar either manic or mixed episode, or schizoaffective disorder manic episode.
  • Minimum score of 20 on the YMRS
  • Written informed consent to participation.

Exclusion Criteria:

  • Patients at immediate risk of committing harm to self or others
  • Use of neuroleptics or mood-stabilisers in the two months preceding admission to EPPIC
  • Organic mental disease, including mental retardation
  • History of clinically significant illness (liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological or metabolic disturbances).
  • Clinically relevant biochemical or hematological abnormalities.
  • Pregnant or lactating woman
  • History of epilepsy
  • History of severe drug allergy or hypersensitivity
  • Non fluency in English.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00202293

Contacts
Contact: Karen T Hallam +61 03 9342-2800 ext 2979 Karen.Hallam@mh.org.au
Contact: Nellie Lucas +61 03 9342-2800 Nellie.Lucas@mh.org.au

Locations
Australia, Victoria
ORYGEN Youth Health Recruiting
Parkville, Victoria, Australia, 3052
Contact: Karen T Hallam    +61 (03) 9342-2800 ext 2979    Karen.Hallam@mh.org.au   
Contact: Nellie Lucas    +61 (03) 9342-2800    Nellie.Lucas@mh.org.au   
Principal Investigator: Michael Berk         
Sub-Investigator: Nellie Lucas         
Sub-Investigator: Craig Macneil         
Sub-Investigator: Melissa Hasty         
Sub-Investigator: Linda Kader         
Sub-Investigator: Karen Hallam         
Sponsors and Collaborators
Melbourne Health
Investigators
Principal Investigator: Philippe Conus ORYGEN Youth Health & Department of Psychiatry, The University of Lausanne
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00202293     History of Changes
Other Study ID Numbers: 2001.013
Study First Received: September 14, 2005
Last Updated: September 14, 2005
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Melbourne Health:
Bipolar
Mania
Drug treatment
First episode
Psychosis
Therapy
Antipsychotic

Additional relevant MeSH terms:
Bipolar Disorder
Psychotic Disorders
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Chlorpromazine
Olanzapine
Lithium
Lithium Carbonate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014