What is the best Selective Serotonin Reuptake Inhibitor (SSRI) for Methamphetamine Use Disorder?

No SSRI is Specifically Recommended for Methamphetamine Use Disorder

There is no evidence supporting any specific SSRI as an effective treatment for methamphetamine use disorder. In fact, available evidence suggests SSRIs may be ineffective or potentially harmful in this population.

Current Evidence on SSRIs for Methamphetamine Use Disorder

• Research specifically examining SSRIs for methamphetamine use disorder shows concerning results:
  • Sertraline has been associated with sustained craving and increased methamphetamine use during treatment compared to placebo 1
  • Poor outcomes with sertraline suggest that serotonergic enhancement may not be beneficial for methamphetamine addiction 1

Alternative Pharmacological Approaches

Instead of SSRIs, consider these evidence-based alternatives:

1. Mirtazapine (non-SSRI antidepressant):

   • Likely results in small reduction in continued methamphetamine use among cisgender men and transgender women 2
   • Does not significantly improve treatment retention or depression symptoms 2

2. Citicoline (nutritional supplement):

   • Shown to have antidepressant properties in patients with methamphetamine dependence and comorbid depression 3
   • Associated with greater treatment retention compared to placebo 3

Non-Pharmacological Approaches

The strongest evidence supports behavioral interventions:

• Contingency Management:
  • Most effective intervention for reducing methamphetamine use 4
  • 20 out of 21 studies showed positive effects on abstinence 4
  • Additional benefits include higher utilization of other treatments and medical services, and reductions in risky sexual behavior 4

Treatment Considerations for Comorbid Conditions

If treating comorbid anxiety or depression in patients with substance use disorders:

• Avoid benzodiazepines as recommended by WHO guidelines 5
• Consider buspirone for anxiety, which has a favorable side effect profile 5
• For depression with substance use disorders, consider:
  • CBT as a preferred psychotherapeutic approach 5
  • Problem-solving therapy to address depressive symptoms 5

Caution with SSRIs in Substance Use Disorders

When using SSRIs in patients with substance use disorders (for comorbid conditions, not for the substance use disorder itself):

• Be aware that SSRIs can cause withdrawal syndrome characterized by dizziness, fatigue, sensory disturbances, anxiety, and irritability 6
• Monitor for potential drug interactions, especially with substances that affect serotonin levels, to prevent serotonin syndrome 6
• SSRIs may cause neonatal withdrawal in pregnant women 6

Clinical Algorithm for Methamphetamine Use Disorder Treatment

1. First-line: Implement contingency management behavioral intervention 4
2. Consider adding:
   • Mirtazapine (15-30mg daily) for patients with continued use despite behavioral interventions 2
   • Citicoline (2000mg/day) particularly for patients with comorbid depression 3
3. For comorbid conditions:
   • Depression: CBT and/or non-SSRI antidepressants
   • Anxiety: Buspirone rather than benzodiazepines 5
4. Avoid: SSRIs specifically for methamphetamine use disorder, as they may worsen outcomes 1

Remember that methamphetamine use disorder treatment requires consistent monitoring, regular assessment of substance use patterns, and adjustment of the treatment plan based on response.