Clinical trial NCT00664976: Treatment Resistant Depression in Bipolar Disorder - A Randomized Controlled Trial of Electroconvulsive Therapy
Official title: Treatment Resistant Depression in Bipolar Disorder - A Randomized Controlled Trial of Electroconvulsive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bipolar Disorder
Keywords: bipolar depression
Electroconvulsive therapy
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Helse Vest
First posted: 2008-04-23
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This project is a randomized controlled trial of electroconvulsive therapy (ECT) compared to treatment as usual (TAU) in the treatment of treatment resistant depression (TRD) in bipolar disorder. The purpose of the trial is to document the effect size, relative effect size and adverse effects of ECT in this condition. A specific purpose is to gain more knowledge about the effect on cognitive function.

Detailed description: This project is a randomized controlled trial of electroconvulsive therapy (ECT) compared to treatment as usual (TAU) in the treatment of treatment resistant depression (TRD) in bipolar disorder. The purpose of the trial is to document the effect size, relative effect size and adverse effects of ECT in this condition. A specific purpose is to gain more knowledge about the effect on cognitive function.

In a national collaboration project the investigators will compare the antidepressant and cognitive effects of ECT with the effects of a drug treatment in use for this condition; a treatment algorithm combining antidepressants, mood stabilizer and antipsychotic drugs. The investigators will use a neuropsychological test battery to disclose possible ECT induced changes in cognitive function, and investigate any long-lasting changes.

In addition, several studies have implemented inflammatory processes in the pathogenesis of depression; inflammatory processes will be examined as a function of changes in clinical status and of treatment modality.

The study is a national collaboration, using the Bipolar Research And Innovation Network- BRAIN, and all the patients are included in the BRAIN-study. The study is funded by Helse Vest RHF, Regional research network on mood disorders (MoodNet) and Norwegian hospitals.

Eligibility criteria: Inclusion Criteria:

* ECT indicated
* Diagnosis of DSM-IV-TR of Bipolar I or Bipolar II disorder as verified by the semi-structured diagnostic interviews SCID or MINI plus.
* Severity: meet DSM-IV-TR criteria of depressive episode, MADRS of 25 or above.
* Treatment resistance
* None response to two trials (during lifetime) with mood stabilizer with proven efficacy in bipolar depression (lithium, lamotrigine, quetiapine, olanzapine) and /or antidepressants.
* A trial is defined as at least 6 weeks in adequate or tolerated dose as reported by the patient, or patients that have been unable to comply with 6 weeks trials of mood stabilizer or an antidepressant.
* Less than 50% reduction in MADRS values or still meet DSM -IV-TR criteria of depressive episode
* Inpatients the first week after start of treatment condition
* The patient are to be treated by the psychiatrist at the hospital for the whole duration of the study (6 weeks)
* Age ≥ 18
* Patient competent to give informed consent according to the judgement of the clinician
* Written informed consent
* Patient fluent in Norwegian language

Exclusion Criteria:

* Earlier ECT nonresponse
* ECT within the last six months
* More than four failed adequate medication trials in the current episode
* Rapid cycling bipolar disorder (e.g.4 or more episodes per year)
* Use of medication or substances (such as pethidine, alcohol, drugs) incompatible with drug medication or ECT. Such medication must be stopped a least 5 half-lives before inclusion in the study.
* Current use of all other psychotropic medication 5 t1/2 before inclusion and during the study period with the exception of the following:
* The use of alimemazine (max dose 30 mg daily), chlorpromazine (max dose 25 mg x 2 daily) and chlorprotixen (max dose 20 mg x 2) is allowed. The use of mianserin (max dose 10 mg daily) is allowed. Such medication has to been discontinued at least 2 days prior neuropsychological assessment. Medication related to the ECT procedure is allowed.
* Inability to comply with study protocol
* Unstable serious medical conditions, including clinically relevant laboratory abnormalities
* Conditions that affect neuropsychological assessment such as Parkinson's Disease, Multiple sclerosis, stroke, alcohol and substance abuse or dependence (according to SCID or DSM-IV-TR)
* Pregnancy or lactation
* Fertile women without adequate contraception (Adequate contraception includes: abstinence, oral contraceptives, intrauterine devices, barrier method)
* YMRS of 20 or more
* Patient at high suicidal risk according to clinicians' judgment

Primary outcomes:
measure: Improvement in depression
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital, Østmarka sykehus
Study officials:
affiliation: NTNU; Helse Vest RHF
name: Arne Vaaler, MD PhD
role: STUDY_DIRECTOR
References:
citation: Schoeyen HK, Kessler U, Andreassen OA, Auestad BH, Bergsholm P, Malt UF, Morken G, Oedegaard KJ, Vaaler A. Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. Am J Psychiatry. 2015 Jan;172(1):41-51. doi: 10.1176/appi.ajp.2014.13111517. Epub 2014 Oct 31.
citation: Bjoerke-Bertheussen J, Schoeyen H, Andreassen OA, Malt UF, Oedegaard KJ, Morken G, Sundet K, Vaaler AE, Auestad B, Kessler U. Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study. Bipolar Disord. 2018 Sep;20(6):531-538. doi: 10.1111/bdi.12594. Epub 2017 Dec 21.
citation: Kessler U, Schoeyen HK, Andreassen OA, Eide GE, Malt UF, Oedegaard KJ, Morken G, Sundet K, Vaaler AE. The effect of electroconvulsive therapy on neurocognitive function in treatment-resistant bipolar disorder depression. J Clin Psychiatry. 2014 Nov;75(11):e1306-13. doi: 10.4088/JCP.13m08960.
citation: Kessler U, Schoeyen HK, Andreassen OA, Eide GE, Hammar A, Malt UF, Oedegaard KJ, Morken G, Sundet K, Vaaler AE. Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression. BMC Psychiatry. 2013 Apr 4;13:105. doi: 10.1186/1471-244X-13-105.
citation: Kessler U, Vaaler AE, Schoyen H, Oedegaard KJ, Bergsholm P, Andreassen OA, Malt UF, Morken G. The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder. BMC Psychiatry. 2010 Feb 23;10:16. doi: 10.1186/1471-244X-10-16.