Contact information
Type
Scientific
Primary contact
Dr Grigori Joffe
ORCID ID
Contact details
Hospital of Kellokoski
Kellokoski
04500
Finland
+358 (0)40 5136500
grigori.joffe@kolumbus.fi
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
7183
Study information
Scientific title
Acronym
Study hypothesis
Mirtazapine will improve negative, possibly positive and extrapyramidal symptoms, as well as neurocognition, if added to a conventional antipsychotic.
Ethics approval
Approved by the Republican Commision on Medical Ethics, Petrozavodsk (Session #6, Sept 9, 2004)
Study design
Double-blind, placebo-controlled trial with an open-label extension phase
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Schizophrenia
Intervention
Add-on mirtazapine versus placebo.
Intervention type
Drug
Phase
Not Specified
Drug names
Mirtazapine
Primary outcome measures
Positive and negative syndrome scale (PANSS) total scores.
Secondary outcome measures
1. Number of responders (20% or more decline on PANSS total or subscores)
2. Change in standard neurocognitive tests
Overall trial start date
10/10/2004
Overall trial end date
31/12/2006
Reason abandoned
Eligibility
Participant inclusion criteria
Male 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
1. 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 patients 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
Recruitment start date
10/10/2004
Recruitment end date
31/12/2006
Locations
Countries of recruitment
Finland
Trial participating centre
Hospital of Kellokoski
Kellokoski
04500
Finland
Sponsor information
Organisation
Stanley Medical Research Institute (USA)
Sponsor details
5430 Grosvenor Lane
Suite 200
Bethesda
MD 20814-2142
United States of America
+1 301 571 0760 ext 124
herrerax@stanleyresearch.org
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Stanley Medical Research Institute
Alternative name(s)
SMRI
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22750079
Publication citations
-
Results
Stenberg JH, Terevnikov V, Joffe M, Tiihonen J, Chukhin E, Burkin M, Joffe G, Predictors and mediators of add-on mirtazapine-induced cognitive enhancement in schizophrenia--a path model investigation., Neuropharmacology, 2013, 64, 248-253, doi: 10.1016/j.neuropharm.2012.06.028.