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

NCT00202293 | Completed Phase 4

• 1 other identifier: 2001.013
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder; Schizoaffective Disorder

Keywords

Bipolar; Mania; Drug treatment; First episode; Psychosis; Therapy; Antipsychotic

Outcome Measures

Primary Outcomes (7)

• Intensity of side effects

  Intensity of side effects

  8 weeks

• ¨The frequency of treatment-emergent adverse events (events that first appear or worsen during the study period) will be compared between both groups.

  8 weeks

• ¨The frequency of side effects as rated with the UKU scale will be compared between both groups.

  8 weeks

• ¨Weight gain will be compared between both groups.

  8 weeks

• ¨Frequency of changes in vital signs and laboratory findings will be compared between both groups.

  8 weeks

• Subjective well being

  8 weeks

• ¨Total scores on the DAI and the SWN will be compared between both groups.

  8 weeks

Secondary Outcomes (16)

• Adherence

  8 weeks

• ¨Degree of adherence to the treatment as scored on the MARS will be compared between both groups.

  8 weeks

• Response to treatment

  8 weeks

• ¨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:

  8 weeks

• ¨Primary efficacy analysis will be assessed by comparing the mean change in theYMRS total score.

  8 weeks

Study Arms (2)

Lithium and olanzapine

EXPERIMENTAL

Drug: Olanzapine; Drug: Lithium

Lithium and chlorpormazine

ACTIVE COMPARATOR

Drug: Lithium; Drug: Chlorpromazine

Interventions

Olanzapine DRUG

Lithium and olanzapine

Lithium DRUG

Lithium and chlorpormazine; Lithium and olanzapine

Chlorpromazine DRUG

Lithium and chlorpormazine

Eligibility Criteria

• Age: 15 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Melbourne Health: lead

Study Sites (1)

ORYGEN Youth Health

Parkville, Victoria, 3052, Australia

Location

MeSH Terms

Conditions

Bipolar Disorder; Psychotic Disorders; Mania

Interventions

Olanzapine; Lithium; Chlorpromazine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring

Study Officials

• Philippe Conus

  ORYGEN Youth Health & Department of Psychiatry, The University of Lausanne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2005
• First Posted: September 20, 2005
• Study Start: October 1, 2001
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: August 31, 2018

Record last verified: 2015-11

Locations

AU (1)