Can Phentermine (phentermine) and Topamax (topiramate) affect mood?

Effects of Phentermine and Topiramate on Mood

Yes, phentermine and topiramate can significantly affect mood, with topiramate in particular being associated with depression, anxiety, and other mood disturbances. The combination medication (known commercially as Qsymia) carries risks of mood-related side effects that require careful monitoring.

Mood Effects of Phentermine/Topiramate

Topiramate-Related Mood Effects

• Topiramate has documented effects on the central nervous system that can impact mood in several ways:
  • Depression and mood problems: The FDA drug label specifically lists depression and mood problems as common neuropsychiatric adverse events 1
  • Psychiatric/behavioral disturbances: These are dose-related for patients taking topiramate 1
  • Cognitive dysfunction: Confusion, difficulty with concentration/attention, and memory problems occur in up to 42-56% of patients at higher doses 1

Phentermine-Related Mood Effects

• As a sympathomimetic amine anorectic (stimulant-like medication), phentermine can cause:
  • Irritability as a common side effect 2
  • Insomnia which can secondarily affect mood 2

Combination Effects

• In the CONQUER trial, the phentermine/topiramate combination showed:
  • Depression-related adverse events in 4-7% of patients (dose-dependent)
  • Anxiety-related adverse events in 5-8% of patients (dose-dependent) 3
  • Higher doses (15mg/92mg) had nearly twice the rate of depression and anxiety events compared to lower doses 3

Risk Factors for Mood Disturbances

Certain patients are at higher risk for experiencing mood-related side effects:

• History of depression or mood disorders: Patients with personal or family history of depression should be carefully monitored 4
• Rapid titration: Faster dose increases and higher initial doses are associated with higher incidences of cognitive and mood effects 1
• Drug interactions: Combining with other medications affecting neurotransmitters can increase risk of mood effects
  • Case reports exist of psychosis when phentermine/topiramate is combined with venlafaxine (an antidepressant) 5

Monitoring and Management

For patients taking phentermine/topiramate:

1. Regular monitoring: Assess for mood changes, especially during the first 3 months of treatment 2
2. Dose considerations:
   • Start with lowest effective dose (3.75mg/23mg) and titrate slowly
   • Consider discontinuation if significant mood changes occur
   • Higher doses (15mg/92mg) carry greater risk of mood effects 3
3. Discontinuation approach: If stopping treatment, taper by taking one capsule every other day for at least one week to minimize risk of mood destabilization 6

Special Considerations

• Bipolar disorder: While some case reports suggest topiramate may have mood stabilizing properties in certain patients 7, 8, it is not FDA-approved for this indication and should be used cautiously
• Pregnancy: Both medications are contraindicated in pregnancy, with topiramate being a known teratogen 2, 6
• Medication interactions: Use caution when combining with other CNS-active medications that could compound mood effects 1

Conclusion

When prescribing phentermine/topiramate for weight loss, clinicians should:

1. Screen for history of mood disorders
2. Inform patients about potential mood-related side effects
3. Monitor regularly for emergence of depression, anxiety, or other mood changes
4. Consider dose reduction or discontinuation if significant mood disturbances occur

The risk of mood effects appears dose-dependent, with higher doses carrying greater risk of psychiatric adverse events.