Efficacy of add-on mirtazapine on clinical and neuropsychologic parameters in schizophrenic patients treated with conventional antipsychotics: a double-blind, placebo-controlled trial with an open-label extension phase

ISRCTN ISRCTN00721331
DOI https://doi.org/10.1186/ISRCTN00721331
Secondary identifying numbers 7183
Submission date
19/09/2005
Registration date
25/05/2006
Last edited
20/11/2012
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Mental and Behavioural Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Grigori Joffe
Scientific

Hospital of Kellokoski
Kellokoski
04500
Finland

Phone +358 (0)40 5136500
Email grigori.joffe@kolumbus.fi

Study information

Study designDouble-blind, placebo-controlled trial with an open-label extension phase
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific title
Study objectivesMirtazapine will improve negative, possibly positive and extrapyramidal symptoms, as well as neurocognition, if added to a conventional antipsychotic.
Ethics approval(s)Approved by the Republican Commision on Medical Ethics, Petrozavodsk (Session #6, Sept 9, 2004)
Health condition(s) or problem(s) studiedSchizophrenia
InterventionAdd-on mirtazapine versus placebo.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Mirtazapine
Primary outcome measurePositive and negative syndrome scale (PANSS) total scores.
Secondary outcome measures1. Number of responders (20% or more decline on PANSS total or subscores)
2. Change in standard neurocognitive tests
Overall study start date10/10/2004
Completion date31/12/2006

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit65 Years
SexBoth
Target number of participants40
Key inclusion criteriaMale or female in- or out-patients will be recruited if:
1. They are aged 18-65 years
2. Have schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) (APA, 1994); defined schizophrenia (disorganized, catatonic, paranoid, residual, or undifferentiated) or schizo-affective disorder, depressive type
3. Receiving one or more conventional antipsychotics at cumulative daily dose of at least 400 mg chlorpromazine equivalents (e.g. haloperidol 12 mg daily) (see Table of Antipsychotic Equivalents), which has remained unchanged (also in terms of dosage) during at least 6 last weeks prior to screening baseline (8 weeks for depot antipsychotics).
Table of antipsychotic equivalents (Basire, 2000) oral mg/day: chlorpromazine 100 mg (= 25-50 mg intramuscular (IM) or 250 mg rectal), fluphenazine 2 mg, levomeptromazine - not known, pericyazine 24 mg, perphenazine 8 mg, prochlorperazine 15 mg, promazine 100 mg, thioridazine 100 mg, trifluoperazine 5 mg, benperidol 2 mg, droperidol 4 mg (Short t1/2) or 3 mg IM/intravenous (IV), haloperidol 3 mg or 1.5 mg IM/IV for doses up to 150 mg/day, trifluoperidol 2 mg, flupentixol 2 mg, zuclopentixol 25 mg up to 150 mg/day, pimozide 2 mg (Long t1/2), remoxiprid 75 mg, amisulpride 100 mg, sulpiride 200 mg, loxapine 10 mg depot (mg/week), fluphenazine 5-10 mg (1-12.5 mg), pipothiazine 10 mg (5-12.5 mg), haloperidol 15 mg (5-12.5 mg), flupentixol 10 mg (8-20 mg), zuclopentixol 100 mg (40-100 mg), fluspirilene 2 mg - not fully established.
4. Demonstrating less than optimal clinical outcome i.e. experiencing either positive or negative symptoms (disability due to only general symptoms will be insufficient for inclusion) resulting in the illness of at least moderate severity (i.e. 4, moderately ill, or more on the clinical global impression (CGI), severity item) (Guy, 1970)
5. The clinical condition has remained stable during the last 6 weeks prior to the baseline visit
6. The patient has a level of understanding that enables reasonable cooperation with the investigator and the ability to fulfil the neurocognitive tests
7. The patient has given written informed consent
Key exclusion criteria1. History of allergy or serious adverse events due to mirtazapine
2. Previous lack of response to a trial with mirtazapine in daily doses of 30 mg or more during four or more weeks, added to the patient’s current or earlier conventional antipsychotic medication
3. Previous lack of response to another antidepressant with affinity to postsynaptic (5-hydroxytryptamine) 5HT2 receptors (e.g. mianserine, trazodone, or nefazodone) used in adequate doses during four or more weeks
4. Current atypical antipsychotic medication (e.g. clozapine, risperidone, olanzapine, sertindole, quetiapine, zotepine, ziprasidone, etc.)
5. History of non-response to either clozapine or other atypical antipsychotics
6. Medical or neurological condition or drug treatment that might put patients at serious risk or bias the assessment of their clinical or mental status (e.g. serious unstable physical illness, epilepsy, organic brain syndrome etc.)
7. History of or current bipolar disorder or schizoaffective disorder, bipolar type (patients with schizoaffective disorder, depressive type can participate in the study)
8. Substance addiction or abuse within the last three months prior to screening
9. Clearly predictable poor compliance
10. For females of child-bearing potential: pregnancy, lactation, or inability or unwillingness to use medically acceptable methods of contraception during the study
11. Treatment with any antidepressant, mood stabilizer, regular (i.e. four or more times within 1 week) use of sumatriptan, naratriptan, zolmitriptan, or drugs with similar mechanism of action, or buspiron or drugs with similar mechanism of action - within four weeks (for fluoxetine, six weeks) prior to baseline. Accidental use of the drugs for treatment of migraine listed above is forbidden on the day of clinical assessment before the assessment.
12. Treatment with antipsychotics other than those currently in use within six weeks prior to baseline
13. Treatment with benzodiazepines as follows:
a. Regular use (i.e. four or more times weekly) of any benzodiazepines at any doses during any of the last four weeks prior to baseline, if they have being received for less than two months. However, regular use of benzodiazepines is permitted if they are absolutely necessary and have been received during two or more months prior to baseline in stable daily doses not exceeding 30 mg of diazepam or comparable doses of other benzodiazepines, as determined by the table of equivalents (Bazire, 2000).
b. Accidental use (i.e. three or less times weekly) of benzodiazepines in daily doses exceeding 30 mg of diazepam or comparable doses of other benzodiazepines (see table of equivalents) (i.e. accidental use of 30 mg or less of diazepam or comparable doses of other benzodiazepines is not a criterion for exclusion). Use of benzodiazepines on the day of clinical assessment is forbidden before the assessment.
14. Electroconvulsive therapy (ECT) within three months prior to baseline
15. Any clinically relevant abnormality detected during the physical examination or laboratory screening tests and likely to interfere with the conduct of the study
Date of first enrolment10/10/2004
Date of final enrolment31/12/2006

Locations

Countries of recruitment

  • Finland

Study participating centre

Hospital of Kellokoski
Kellokoski
04500
Finland

Sponsor information

Stanley Medical Research Institute (USA)
Research organisation

5430 Grosvenor Lane
Suite 200
Bethesda
MD 20814-2142
United States of America

Phone +1 301 571 0760 ext 124
Email herrerax@stanleyresearch.org
Website http://www.stanleyresearch.org
ROR logo "ROR" https://ror.org/01pj5nn22

Funders

Funder type

Research organisation

Stanley Medical Research Institute
Private sector organisation / Research institutes and centers
Alternative name(s)
The Stanley Medical Research Institute, SMRI
Location
United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/01/2013 Yes No