Intervention: Amphetamine
Trial phase: Not Applicable
ATC code: N06BA01 | N06BA02
SMILES: CC(N)Cc1ccccc1
Sex: All
Age groups: Adult
Healthy volunteers: No
Participants at risk: 2
Group description: In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine.

Amphetamine-dextroamphetamine (AMPH): The amphetamine-dextroamphetamine will be in a pill formulation. The dosage of the amphetamine-dextroamphetamine will be flexibly adjusted up or down by a study clinician based on the participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon.

Well-being therapy: Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.
Eligibility criteria:
Inclusion Criteria

Outpatients between 18 and 60 years of age.
Experiencing residual symptoms after 8 weeks of SSRI therapy, with at least 4 weeks at a stable dose of the current agent prior to randomization.
Fulfillment of DSM-IV diagnostic criteria for MDD during the present episode of illness with continuing residual symptoms.
A score of 14 to 26 on the 31-item Hamilton Depression Rating Scale (HAM-D-31) at screening and randomization.
A Clinical Global Impression of Severity (CGI-S) score of 3 or 4 at screening and randomization.

Exclusion Criteria

Treatment within 4 weeks of randomization with any non-SSRI antidepressant, antipsychotic, mood stabilizer, standing benzodiazepine, stimulant, or stimulant-like agent.

Allowed exception 1: Concomitant benzodiazepines, at a stable dose, that have been taken for at least one year with no history of abuse.
Allowed exception 2: Effexor, duloxetine (Cymbalta) or milnacipran (Savella) can serve as main SSRI treatment.
Allowed exception 3: Combinations of SSRIs (ex. Zoloft & Lexapro concomitantly) are acceptable as main SSRI treatment.
If a subject endorses "yes" or "agree" of any item from 12 to 23 on the CHRT, it would indicate active suicidality and would be exclusionary.
Significant suicide risk.
Current treatment-resistant episode of MDD.
A primary diagnosis of an Axis I disorder other than MDD.
History of a psychotic disorder, dysthymia, antisocial personality disorder, BPD, or mental retardation.
History of a substance use disorder, with the exception of nicotine dependence, within 12 months prior to screening.
History of stimulant abuse, prescription drug abuse, and eating disorders.
Initial insomnia at screening that is not adequately controlled by medications. Subjects with recent history of unstable insomnia as defined by active or poorly controlled symptoms of insomnia within the past 1 month will be excluded.
Co-morbid medical conditions including a structural heart defect or rhythm abnormality that might be exacerbated by stimulant therapy; hypertension as measured by a resting sitting systolic blood pressure of > 149mmHg or diastolic blood pressure > 95mmHg; tachycardia as measured by a sitting pulse rate of >100 bpm or <50 bpm after resting for 5 minutes.
Allergy, hypersensitivity, intolerance, or history of non-responsivity to stimulant medications.
History of non-responsivity to CBT or well-being therapy.
Women who are pregnant or breastfeeding.
Glaucoma or hyperthyroidism
Current concomitant therapy is only permitted if it is supportive therapy (not specifically CBT) and has been ongoing for at least one year. However, if a subject has been in therapy for less than one year and wishes to discontinue or take a hiatus from their current therapy before coming in for a screening visit, this will be allowed. Additionally, subjects may not enter into other talk therapies for the duration of this study.