Cycloserine ($ generic but high price)
Antibiotic (50-150 mg: enhances learning as glutamate agonist; Over 500mg: treats depression as glutamate antagonist)
- Treatment resistant depression4
- Enhances exposure therapy for anxiety
- Enhances TMS therapy1
Features
Dosing
Depression 500 mg bid (start 250mg 1 qhs and raise by 250mg every 4-7 days).
Augment exposure therapy: 50-150 mg 1-2 hour before exposure exercise.
Augment TMS: 100 mg 1-2 hours before treatment for first 2 weeks of TMS or iTBS.
Give with vitamin B6 200 mg/day to reduce side effects (eg, tremor).
COMPOUNDING DOSE: d-cycloserine is only available from specialty or independent pharmacies (special order) and expensive ($30/pill). It only comes as 250 mg capsule, so use a compounding pharmacy to repackage those as 100 mg (or microdose at home). This lower dose range works better for neuroplasticity in TMS/therapy because higher doses have opposite effects on glutamate.
Management
D-cycloserine is an old anti-tubercular agent from the 1950’s. Its antidepressant effects were first discovered in the 1960’s. Low dose is well tolerated. Higher dose (> 600 mg) have ketamine-like effects including mental status change.
TOLERABILITY: Well tolerated at low doses. At high doses, the most common side effects are dizziness (14%), headache (12%), visual changes (4%), tinnitus (5%), tremor, and drowsiness. Neurologic side effects are improved by taking it with vitamin B6 (200 mg qd).
RISKS: At high doses, psychosis, delirium, seizures, rare reports of congestive heart failure.
EMR Text
Augmentation of Exposure Therapy
Low-dose d-cycloserine use based on multiple randomized trials where it enhanced the effects of exposure therapy for anxiety disorders, including phobia, social anxiety, PTSD, and OCD (in low doses it enhances neuroplasticity and learning) (Rosenfield D et al, J Anxiety Disord 2019;68:102149).
Side effects of low-dose d-cycloserine reviewed with patient.
Augmentation of TMS
Low-dose d-cycloserine use based on a randomized trial where it increased remission rates from TMS 10-fold when taken for 2 weeks before each TMS session (enhancing neuroplasticity) (Cole J et al, JAMA Psychiatry 2022, 79(12):1153-1161).
Side effects of low-dose d-cycloserine reviewed with patient.
Treatment resistant depression
D-cycloserine use based on small randomized controlled trials where high doses (600-1,000 mg) reduced treatment-resistant depression (high doses act as glutamate angatonists, similar to ketamine) (Heresco-Levy U et al, Int J Neuropsychopharmacol 2013;16(3):501-506).
Side effects of low-dose d-cycloserine, including psychosis and seizures, reviewed with patient.