A Pilot Study of Citicoline add-on Therapy in Patients With Bipolar Disorder or Major Depressive Disorder and Amphetamine Abuse or Dependence

Study Overview
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Brief Summary
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Bipolar disorder (BD) is a common and severe psychiatric illness. Drug and alcohol abuse are very common in people with BD and other mood disorders and are associated with increased rates of hospitalization, violence towards self and others, medication non-adherence and cognitive impairment. However, few studies have investigated the treatment of dual-diagnosis patients as substance use is frequently an exclusion criterion in clinical trials of patients with BD. To address this need, we have developed a research program that explores the pharmacotherapy of people with BD and substance related-disorders. A potentially very interesting treatment for BD is citicoline. Some data suggest that this supplement may stabilize mood, decrease drug use and craving, and improve memory. We found promising results with citicoline in patients with BD and cocaine dependence. In recent years the use of amphetamine and methamphetamine has become an important public health concern. However, virtually no research has been conducted on the treatment of amphetamine abuse. We propose a double-blind placebo controlled prospective trial of citicoline in a group of 60 depressed outpatients with bipolar disorder, depressed phase or major depressive disorder and amphetamine abuse/dependence, to explore the safety and tolerability of citicoline, and its efficacy for mood symptoms, stimulant use and craving and its impact on cognition. Our goal is to determine which symptoms (e.g. mood, cognition, substance use) citicoline appears to be most effective and estimate effect sizes for future work.

Detailed Description
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Sixty outpatients meeting the inclusion and exclusion criteria will be enrolled after completing an Institutional Review Board (IRB)-approved informed consent process. Baseline evaluation will include a medical and psychiatric history, structured clinical interview for Diagnostic and Statistical Manual (DSM-IV) (SCID), mood assessment with the Inventory of Depressive Symptomatology-Self Report (IDS-C), Young Mania Rating Scale (YMRS), and cognitive assessment with the Hopkins Auditory Verbal Learning Test (HVLT) (similar to the Rey Auditory Verbal Learning Test (RAVLT) but more alternative equivalent versions are available), Stroop and computer assessments including Sternberg Memory Task and the Running Memory Continuous Performance Test. Alternate but equivalent versions of all cognitive tests, except the Stroop, will be used to minimize practice effects with repeated administration. Days and amounts of amphetamine and other substance use will be assessed at each visit with urine drug screens, and through self-report using the timeline follow-back method. Amphetamine, and other drug, craving will be assessed with a visual analogue scales. Citicoline or placebo add-on therapy will be given beginning at one tablet (500mg)/day with an increase to two tablets 1000 mg/day at week 2, three tables 1500 mg/day at week 4 and four tablets 2000 mg/day at week 6.

Official Title
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A Double-blind, Placebo-controlled Pilot Study of Citicoline add-on Therapy in Patients With Bipolar Disorder or Major Depressive Disorder and Amphetamine Abuse or Dependence

Conditions
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Amphetamine Abuse, Amphetamine Dependence, Bipolar Disorder, Major Depressive Disorder

Intervention / Treatment
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* Drug: Citicoline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ages 18-70 years Meeting criteria for a current major depressive episode (bipolar I,II, not otherwise specified (NOS) , depressed phase) or major depressive disorder on the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) with a duration of at least 4 weeks Meeting criteria for amphetamine abuse or dependence with use within 14 days prior to baseline No psychotropic medication changes within 14 days prior to study entry Exclusion Criteria: Pregnant or nursing women Current citicoline therapy Active suicidal or homicidal ideation with plan and intent Dementia, mental retardation or other severe cognitive impairment that might interfere with the informed consent process Currently incarcerated at a prison or jail Severe or life threatening medical condition (e.g. terminal cancer, congestive heart failure)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citicoline<br>Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects. | Drug: Citicoline<br>* Citicoline is an over the counter supplement that may have neuroprotective properties and may have antidepressant effects. Citicoline or placebo (identical in appearance) add-on therapy was given beginning at one tablet (500mg/day) with an increase to two tablets (1000 mg/day) at week 2, three tablets (1500 mg/day) at week 4 and four tablets (2000 mg/day) at week 6. Doses were decreased, if needed, due to side effects.<br>|
| Placebo Comparator: Placebo<br>Placebo matching active medication. | Drug: Placebo<br>* Placebo matching active medication in all other physical aspects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Symptoms | Inventory of Depressive Symptomatology-Clinician Rated (IDS-C), (a clinician-administered depression scale) is used to assess the severity of depressive symptoms.Scores can range from 0 to 84. The higher the score, the worse the depressive symptoms(worse outcome). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amphetamine Craving | Visual Analog Scale (VAS) assessing Methamphetamine craving with a 1-100 scale.Higher values on the VAS scale indicate a higher Methamphetamine craving(worse outcome). | 12 Weeks | 
| Amphetamine Use | Participant reported days per 7-day week of methamphetamine use. | 12 weeks | 
| Hopkins Auditory Verbal Learning Test (HVLT) | The Hopkins Auditory Verbal Learning Test (HVLT) is a measure of cognition (memory/recall). Raw scores are derived for Total Recall, Delayed Recall, Retention (% retained), and a Recognition Discrimination Index. Raw scores are calculated into T-scores. T-scores are standardized scores on each dimension for each type. A score of 50 represents the mean. A difference of 10 from the mean indicates a difference of one standard deviation. Thus, a score of 60 is one standard deviation above the mean, while a score of 30 is two standard deviations below the mean. | 12 weeks | 
| Stroop Color Word Test | The Stroop Color Word Test measures the individual's ability to separate the word and color naming stimuli thus the ability to sort information from the environment and selectively react to this information. The scoring is a measure of time to complete 100 items and the numbers of items that can be completed. THe scores are converted into T-scores which have a mean of 50 and a standard deviation of 10. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amphetamine Abuse, Amphetamine Dependence, Bipolar Disorder, Major Depressive Disorder, Citicoline