Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder.

Major Depressive Disorder Clinical Trial

Official title:

Double-Blind, Placebo-Controlled, Randomized Trial of Adjunctive, Flexibly-Dosed Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment In Major Depressive Disorder (MDD) Partially Responsive to Selective Serotonin Reuptake Inhibitor (SSRI) or Selective Norepinephrine Reuptake Inhibitor (SNRI) Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01148979
• Other study ID #: 2010-P-000871
• Status: Completed
• Phase: Phase 4
• First received: June 21, 2010
• Last updated: September 21, 2015
• Start date: September 2010
• Est. completion date: October 2014

Study information

• Verified date: September 2015
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study aims to test the effect of a newly-approved stimulant medication, lisdexamfetamine (Vyvanse), on specific residual symptoms of depression found in some patients who are undergoing treatment with, but have only partially responded to, a selective-serotonin reuptake inhibitor (SSRI) or selective-norepinephrine reuptake inhibitor (SNRI) antidepressant. Specifically, the investigators hypothesize that symptoms potentially related to deficient dopaminergic activity, such as lassitude, apathy, reduced positive affect and impaired executive function, in particular, will improve. This protocol is designed to test the hypothesis that this cluster of co-occurring residual symptoms sometimes found in treated depression will respond as a group to psychostimulant therapy. The investigators propose to measure this cluster of symptoms in a population of residually depressed subjects demonstrating them, and then to measure the effect of stimulant therapy on this cluster, and each constituent symptom, as well as to measure its effect on subjects' overall functional impairment, and to document treatment emergent adverse effects. The investigators hope to better understand the specific symptoms in this clinical population that are likely to improve with stimulant therapy. The investigators also hope to be able to characterize the side effect burden of stimulant therapy in this clinical population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Meeting diagnostic criteria for major depression during the present episode of illness, currently with at least mild improvement by report (CGI-I =3) but with continuing residual symptoms.

2. A score of =10 on MADRS items 1,2,6,7 and 8, (the MADRS Dysphoric Apathy/Retardation factor, Parker et al., 2003) at screening and randomization. These 5 items are: Apparent sadness, Reported sadness, Concentration difficulties, Lassitude, and Inability to feel. A score of =3 will be required for at least 2 of these items.

3. A score of 3 or 4 on the Clinical Global Impression of Severity (CGI-S) at screening and randomization.

4. At randomization subjects must have received therapeutic dosages of approved SSRI or SNRI agents for at least 8 weeks, with the last 4 weeks at a constant dosage.

5. Females of Child-bearing Potential (FOCP) must have a negative serum beta Human Chorionic Gonadotropin (B-hCG) pregnancy test at the screening visit and a negative urine pregnancy test at the baseline visit, and agree to use one of the following methods of birth control: oral contraceptives, contraceptive implants, injectable contraceptives, IUDs, double-barrier contraception, sexual abstinence or vasectomized partner(s).

Exclusion Criteria:

1. Treatment within 4 weeks of randomization with any non-SSRI/SNRI antidepressant (trazodone is permitted up to 100 mg HS for sleep); any antipsychotic agent; any mood stabilizer; any standing benzodiazepine regimen other than at low doses for sleep (= 1 mg lorazepam HS or the equivalent); or a standing regimen of any other agent that may affect cognitive function (e.g., psychostimulants, including modafinil or R-modafinil).

2. Any current or past psychotic disorder, Bipolar I or II disorder, Current panic disorder, History of ADHD, Antisocial Personality Disorder or Borderline Personality Disorder, Mental retardation or any dementing disorder.

Covi Anxiety Scale score greater than Raskin Depression Scale score at Screening, to exclude subjects with more prominent anxiety than depression

3. MADRS Sleep (item 4), or Appetite (item 5) >3 at screening or randomization

4. Initial insomnia at screening that is not adequately controlled by sleep medication (trazodone up to 100 mg HS for sleep and/or = 1 mg lorazepam HS or the equivalent).

5. Medical conditions that might be exacerbated by Vyvanse treatment, such as uncontrolled hypertension or angina; or conditions that would make study findings hard to interpret, such as hyperthyroidism

6. History of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.

7. Known cardiac structural abnormality or any other condition that may affect cardiac performance

8. Any clinically significant ECG or laboratory abnormality at Screening

9. Current abnormal thyroid function, as defined by abnormal TSH at Screening (Treatment with a stable dose of thyroid medication for at least 3 months is permitted if TSH is normal at screening).

10. Suicide attempt within the past 2 years or a history of any homicidal behavior.

11. MADRS Suicidal thoughts (item 10) >4 at any study visit, or if a patient is considered by the investigator to be at clinical risk of suicide at any time in the course of the study.

12. resting sitting systolic blood pressure >149mmHg or diastolic blood pressure > 95mmHg. Subjects may be on monotherapy with anti-hypertensive medication.

13. documented allergy, hypersensitivity, intolerance, or non-responsivity to methylphenidate or amphetamines.

14. Subject has a history of a substance use disorder (abuse or dependence, as defined by DSM-IV-TR™), with the exception of nicotine dependence, within 6 months prior to screening.

15. Subject has glaucoma

16. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cognition Disorders
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Lisdexamfetamine Dimesylate 20-50 mg
Subjects given 30 mg study drug (Vyvanse vs. matched placebo) at baseline to take each morning. If 30 mg intolerable before next scheduled appointment, they can return to clinic and exchange 30 mg tablets for 20 mg tablets. Visit 3 dosage range is 20-40 mg/d. Now subjects have been taking either 30 or 20 mg of study medication per day. If clinical effects insufficient and side effects tolerable, subject's dose will be raised by 10 mg/d to 30 or 40 mg/d. If subjects receiving more than 20 mg/d experience uncomfortable side effects, their dose may be reduced to 20 mg at that visit. Visit 4 dosage range is 20-50 mg, study drug dose may be moved up or down by 10 mg based on clinical judgment, minimum of 20 mg, maximum of 50 mg/d. Study drug dosage must not change over the last 2 weeks (end of 4 weeks on study drug). Arms: Sugar Pill , Lisdexamfetamine Dimesylate 20-50mg Other Names: Vyvanse

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the dysphoric apathy/retardation sub-factor of Montgomery-Asberg Depression Rating Scale (MADRS).	The study's Primary endpoint will be the change in the dysphoric apathy/retardation sub-factor of Montgomery-Asberg Depression Rating Scale (MADRS), to be administered at every visit.	Weekly, from Baseline to week 4 of treatment	No