Escitalopram efficacy and tolerability in treatment resistant depression. an open study.
The objective of this European multicentre study was to evaluate escitalopram efficacy and tolerability in a population which has been shown to have Treatment Resistant Depression (TRD) in a prospective open treatment phase with venlafaxine over a 6 week period at an adequate dose after non response to previous antidepressants
Lundbeck
417 participants
Jan 1, 2005
Interventional
Conditions
Summary
BACKGROUND: Treatment resistant depression (TRD) is associated with higher dysfunction, morbidity and mortality compared to major depressive disorder and regarded as more difficult and expensive to treat. Despite this there are only few studies that investigate potential treatment strategies. OBJECTIVE: The objective of this European multicentre study was to evaluate escitalopram efficacy and tolerability in a population which has been shown to have TRD in a prospective open treatment phase with venlafaxine over a 6 week period at an adequate dose after non response to previous antidepressants. METHODS: Four hundred seventeen patients, who failed to respond to a previous retrospectively assessed antidepressant, were firstly included in a 6-week venlafaxine treatment; secondly, those who failed to respond to venlafaxine were treated for further 6 weeks with escitalopram.
Eligibility
Inclusion Criteria1
- To be included in the 6 week prospective treatment with venlafaxine each patient had to: 1. be able to read and understand the patient information sheet; 2. have signed the informed consent form; 3. be an in- or outpatient, male or female, of at least 18 years of age; 4. have a Current Major Depressive Episode, assessed with the Mini International Neuropsychiatric Interview (MINI), moderate or severe, according to DSM-IV-TR criteria (classification codes: 296.2x or 296.3x); 5. have been treated for the Current Episode with any antidepressant (AD1) (other than escitalopram or venlafaxine) prescribed continuously at its optimal dose (Annex 1) for at least 4 weeks (criterion verified at screening) – if at inclusion the patient was not during AD1 period of any antidepressant, this period without antidepressant should not have exceeded 4 weeks); 6. be a non-responder to this previous treatment (AD1) (Montgomery Asberg Depression Rating Scale (MADRS) improvement <50%); 7. have a total score equal or above 22 on the MADRS.
Exclusion Criteria1
- To be excluded from the study each patient had to: 1. have previously participated in this study; 2. be a non responder to a combination of 2 antidepressants (at least 2 weeks of treatment with an adequate dose for each of the 2 drugs) and/or to an augmentation therapy (at least 2 weeks with a potentiating agent at any dose) at the time of screening; 3. have a history of severe drug allergy or hypersensitivity, or known hypersensitivity to escitalopram or venlafaxine; 4. have one or more of the following conditions: a. any Current Psychiatric Disorder established as the principal diagnosis other than Major Depressive Disorder as defined in the DSM-IV-TR (assessed with the MINI); b. any Substance Disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR; c. any severe Personality Disorder according to investigator clinical judgement that might compromise the study; 5. have received one or more of the following disallowed treatments: a. oral antipsychotic drugs had to have been stopped at least 2 weeks before inclusion; the patient could be included if the antipsychotic medication had been taken at infra-therapeutic dose (lower than the recommended dose as indicated in the notice of the product); patients were excluded if they had received a depot antipsychotic preparation within the past 6 months; b. ECT within the past 6 months; c. lithium, carbamazepine, lamotrigine, valproate or valpromide at therapeutic dose and for more than 2 weeks within the past month; d. benzodiazepines: more than 25 mg/day of diazepam or equivalent within the last week for chronic users of benzodiazepines (more than 3 months on treatment) and more than 10 mg/day of diazepam or equivalent for non chronic users (less than 3 months); e. more than 20 mg/day of zolpidem, 15 mg/day of zopiclone or 20 mg/day of zaleplon within the last week; f. any non-benzodiazepine anxiolytic within the last week; g. any serotonin agonist (e.g., triptans) within the last week; h. any other drug with potential psychotropic effects within the last week; i. any investigational product within 3 months prior to screening; j. escitalopram or venlafaxine at adequate dose and duration during the Current Episode; k. formal psychotherapy started in the month preceding inclusion; 6. have a previous history of convulsive disorder other than a single childhood febrile seizure; 7. present evidence of urinary retention or glaucoma; 8. have a serious illness and/or serious sequelae thereof, including liver or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance; 9. have, in the opinion of the investigator (based on physical examination, medical history and vital signs), comorbid conditions(s) that would render inclusion in the study unsafe; 10. take medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy; 11. in female patients, be pregnant or breastfeed at inclusion as well as during the study; 12. be, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any reason.
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Interventions
Patients meeting the entry criteria and for whom the investigator considered switching to venlafaxine, were included in a 6 week prospective treatment with venlafaxine (AD2) prescribed continuously at its optimal dose. Initial venlafaxine oral tablets daily dose was 75 mg; the daily dose could be further increased to 150 mg after 1 week, on the basis of an unsatisfactory response as judged by the investigator. If necessary, the dose could be increased up to a maximum of 225 mg. Escitalopram Treatment Patients considered as non responders at the end of the venlafaxine treatment were evaluated for inclusion in the second phase of the trial. To be eligible for inclusion in the 6-week prospective treatment with escitalopram (AD3) each patient had to meet 1 of the 2 following inclusion criteria: 1. At day 28: the patient has a total score =20 on the MADRS and a decrease from start of the venlafaxine treatment in Montgomery–Asberg Depression Rating Scale (MADRS) total score <25%; 2. At day 42: patient has a total score equal or more than 20 on the MADRS or a decrease from start of the venlafaxine treatment in MADRS total score <50%. Exclusion Criteria: any patient who met the following criteria at the end of the venlafaxine treatment was not included in the escitalopram treatment: 1. The patient had not taken AD2 medication for three consecutive days or more, or overall compliance was less than 80% during the venlafaxine treatment; 2. any of the previously described exclusion criteria that appeared since the initiation of the venlafaxine treatment. Initial escitalopram oral tablets daily dose was 10 mg; the daily dose had to be increased to 20 mg after 1 week; after 2 weeks, the daily dose could be further increased to 30 mg on the basis of an unsatisfactory response as judged by the investigator.
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ACTRN12613000256774