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IRCT20200317046801N3 IRCT 2026-11-06 Karaj University of Medical Sciences Effect of Amantadine as Adjunctive Therapy on Depression and Cognitive Impairment in Bipolar Depression Title : The efficacy of amantadine as an adjunctive therapy in treating depression and cognitive impairment in patients with bipolar depression at Imam Hossein, Shariati, andImam Ali hospitals in Karaj a randomized double-blind placebo-controlled clinical trial 2026-12-22 anticipated 64 Pending https://irct.ir/trial/94593 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Treatment, Other design features: This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial with a 1:1 allocation ratio. Block randomization (block size of 4) will be used. Participants will receive either amantadine 100 mg daily or placebo, in addition to standard lithium therapy, for 12 weeks. The primary outcome measures will be assessed at baseline and weeks 4, 8, and 12, Randomization description: Randomization will be performed using a block randomization method with fixed block sizes of four (1:1 allocation ratio). The unit of randomization is the individual patient. The randomization sequence will be generated by a statistician independent of the research team using computer-generated random numbers (e.g., Random Allocation Software). Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes (SNOSE) prepared by the same independent person. Each envelope will contain the allocation code (amantadine or placebo) and will be opened by the clinical investigator only after the participant has been enrolled, completed baseline assessments, and signed the informed consent form. No stratification will be applied, Blinding description: This study is a double-blind trial. Participants, clinical caregivers (psychiatrists and nurses responsible for patient care), the principal investigator and research team, outcome assessors, and the data analyst will all be blinded to treatment allocation. Amantadine and placebo will be provided as identical capsules in terms of appearance, size, color, and packaging, prepared by the hospital pharmacy under a code. Neither the participants nor any member of the research team will know which treatment a participant is receiving. The randomization codes will be kept by an independent person outside the research team and will be revealed only after the statistical analysis is complete, or in case of a medical emergency requiring unblinding. The data analyst will receive coded group labels (A/B) and will perform the analysis without knowledge of the actual treatment. 3 Bipolar depression. Intervention 1: Intervention group: Intervention group: Lithium carbonate with a target serum level of 0.8 to 1.2 milliequivalent per liter (starting dose of 300 milligrams three times daily, titrated by the treating psychiatrist to a final dose of 900 to 1200 milligrams per day) plus amantadine capsule 100 milligrams daily for 12 weeks. Amantadine and placebo capsules are identical in appearance, size, color and packaging and are prepared by the hospital pharmacy. Patients take one capsule orally each day. Intervention 2: Control group: Control group: Lithium carbonate with a target serum level of 0.8 to 1.2 milliequivalent per liter (starting dose of 300 milligrams three times daily, titrated by the treating psychiatrist to a final dose of 900 to 1200 milligrams per day) plus placebo capsule daily for 12 weeks. Placebo capsules are identical in appearance, size, color and packaging to amantadine capsules and are prepared by the hospital pharmacy. Patients take one capsule orally each day. Yes - There is a plan to make this available What will be shared: De-identified individual participant data (IPD) underlying the primary and secondary outcomes, study protocol, statistical analysis plan, informed consent form, analysis codes, and data dictionary. When: Access will begin 6 months after publication of the main results and will remain available for 5 years. To whom: Researchers affiliated with academic or scientific institutions. Conditions: Data will be shared for non-commercial research purposes, including re-analysis and verification of published results. Requesters must sign a data access agreement and agree not to attempt re-identification of participants. Where to obtain: Requests should be sent to the principal investigator, Dr. Rahim Badrfam, at the Clinical Research Development Unit of Imam Hossein Hospital, Alborz University of Medical Sciences, Karaj, Iran. Email:rbadrfam@gmail.com How to obtain: The request will be reviewed by the principal investigator and the Clinical Research Development Unit within 2 weeks. If approved, a data access agreement will be sent to the requester. Upon signing the agreement, the de-identified data will be transferred securely within 4 weeks. Comments:
public Rahim Badrfam
Shariati Hospital, Emam Khomeini Blvd., Jafar Abad, Mahdasht Road, Karaj, Alborz, Iran
Karaj Iran (Islamic Republic of) 3184945611 +98 26 3730 5001 rbadrfam@gmail.com Karaj University of Medical Sciences scientific Rahim Badrfam
Shariati Hospital, Emam Khomeini Blvd., Jafar Abad, Mahdasht Road, Karaj, Alborz, Iran
Karaj Iran (Islamic Republic of) 3184945611 +98 26 3730 5001 rbadrfam@gmail.com Karaj University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Age between 30 and 60 years ) Diagnosis of bipolar disorder type I or II in an active depressive episode based on DSM-5-TR criteria confirmed by two psychiatrists Ability to read and write BDI-II score ≥ 20 (active depression Written informed consent obtained from the patient and their guardian 30 years 60 years Both Age < 30 or > 60 years Inability to read and write BDI-II score < 20 Inappropriate serum lithium level (>0.8 or <1.2 mEq/L) in patients receiving lithium ECT treatment within the past 2 months Alcohol or illicit substance use within the past 3 months (confirmed by urine test) Known hypersensitivity to amantadine Active major comorbid psychiatric disorder: Active PTSD, Cluster B personality disorder (especially borderline and antisocial), Active psychosis (schizophrenia, schizoaffective disorder) Active neurological diseases (epilepsy, Parkinson's disease, MS, dementia) Severe liver disease (Child-Pugh C), renal failure (GFR < 30 ml/min), unstable cardiovascular disease Pregnancy, breastfeeding, or lack of effective contraception Concomitant use of MAO inhibitors or strong anticholinergic drugs (e.g., trihexyphenidyl) History of seizure or epilepsy F31.3 Bipolar disorder, current episode depressed, mild or moderate severity Treatment - Drugs Treatment - Drugs Intervention group: Intervention group: Lithium carbonate with a target serum level of 0.8 to 1.2 milliequivalent per liter (starting dose of 300 milligrams three times daily, titrated by the treating psychiatrist to a final dose of 900 to 1200 milligrams per day) plus amantadine capsule 100 milligrams daily for 12 weeks. Amantadine and placebo capsules are identical in appearance, size, color and packaging and are prepared by the hospital pharmacy. Patients take one capsule orally each day. Control group: Control group: Lithium carbonate with a target serum level of 0.8 to 1.2 milliequivalent per liter (starting dose of 300 milligrams three times daily, titrated by the treating psychiatrist to a final dose of 900 to 1200 milligrams per day) plus placebo capsule daily for 12 weeks. Placebo capsules are identical in appearance, size, color and packaging to amantadine capsules and are prepared by the hospital pharmacy. Patients take one capsule orally each day. Severity of depression. Timepoint: At baseline (before intervention) and at weeks 4, 8 and 12 after starting the intervention. Method of measurement: Beck Depression Inventory, second edition. Cognitive function. Timepoint: At baseline (before intervention) and at weeks 4, 8 and 12 after starting the intervention. Method of measurement: Neuropsychiatry Unit Cognitive Assessment Tool, Trail Making Test parts A and B, and Wisconsin Card Sorting Test. Depression response rate, defined as a 50 percent or greater reduction in Beck Depression Inventory second edition score from baseline to week 12. Timepoint: At baseline (before intervention) and at week 12 after starting the intervention. Method of measurement: Beck Depression Inventory, second edition. Depression remission rate, defined as Beck Depression Inventory second edition score below 10 at week 12. Timepoint: At week 12 after starting the intervention. Method of measurement: Beck Depression Inventory, second edition. Cognitive response rate, defined as a 50 percent or greater increase in Neuropsychiatry Unit Cognitive Assessment Tool score from baseline to week 12, or a 50 percent reduction in Trail Making Test part B duration, or improvement in Wisconsin Card Sorting Test performance. Timepoint: At baseline (before intervention) and at week 12 after starting the intervention. Method of measurement: Neuropsychiatry Unit Cognitive Assessment Tool, Trail Making Test parts A and B, and Wisconsin Card Sorting Test. Frequency of adverse drug effects. Timepoint: At weeks 4, 8 and 12 after starting the intervention. Method of measurement: Clinical interview and physical examination by the treating psychiatrist. Karaj University of Medical Sciences Approved 2026-10-24 Ethics committee of Alborz University of Medical Sciences Faculty of Medicine, above the University of Art, West Bu Ali Street, s,Nabuwwat,karaj,, Karaj Alborz Iran (Islamic Republic of)