What selective serotonin reuptake inhibitor (SSRI) can be used with Qsymia (phentermine and topiramate)?

SSRI Selection with Qsymia

Sertraline is the preferred SSRI to use with Qsymia (phentermine-topiramate), as this combination has been specifically evaluated and is not absolutely contraindicated, though it requires careful cardiovascular and serotonergic monitoring. 1

Primary Recommendation

• The combination of phentermine-topiramate and sertraline can be safely prescribed together with appropriate monitoring for cardiovascular parameters (blood pressure and heart rate) and serotonergic effects 1
• This combination is explicitly discussed in clinical guidance as feasible, unlike MAO inhibitors which are absolutely contraindicated within 14 days of phentermine use 1

Key Safety Considerations

Serotonin Syndrome Risk

• Phentermine has sympathomimetic properties that include some serotonergic stimulation, creating theoretical concerns when combined with SSRIs 1
• Caution is required when combining two or more serotonergic drugs, including SSRIs with stimulants like phentermine 2
• Start the SSRI at a low dose, increase slowly, and monitor closely for serotonin syndrome symptoms in the first 24-48 hours after any dosage changes 2
• Serotonin syndrome symptoms include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2

Cardiovascular Monitoring Requirements

• Monitor blood pressure and heart rate at baseline and regularly throughout treatment, especially during the first 12 weeks 1
• Phentermine causes modest increases in heart rate and blood pressure through sympathetic nervous system activation 1
• SSRIs, particularly citalopram, may interact with drugs that prolong the QT interval 2

Alternative SSRI Considerations

If Sertraline is Not Suitable

• Citalopram or escitalopram may be preferred alternatives as they have the least effect on CYP450 isoenzymes compared with other SSRIs and lower propensity for drug interactions 2
• However, citalopram carries QT prolongation risk at doses exceeding 40 mg/day and should be avoided in patients with long QT syndrome 2

SSRIs to Approach with Greater Caution

• Fluvoxamine has greater potential for drug-drug interactions through multiple CYP450 pathways (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6) 2
• Paroxetine has been associated with increased risk of suicidal thinking compared to other SSRIs 2
• Fluoxetine, paroxetine, and sertraline may interact with drugs metabolized by CYP2D6 2

Implementation Protocol

Starting the Combination

• Begin Qsymia at 3.75 mg/23 mg once daily for 14 days, then advance to maintenance dose of 7.5 mg/46 mg daily 1
• Take Qsymia early in the day to minimize insomnia 1
• Start the SSRI at a subtherapeutic "test" dose to assess tolerance, as SSRIs can initially cause anxiety or agitation 2
• Increase SSRI dose slowly at 1-2 week intervals for shorter half-life agents like sertraline 2

Ongoing Monitoring

• Check blood pressure and heart rate at every visit 1
• Monitor for serotonin syndrome symptoms, particularly after dose adjustments 2
• Discontinue Qsymia if less than 5% weight loss after 12 weeks at maximum dose 1

Critical Contraindications

Absolute Contraindications to This Combination

• Never combine Qsymia with MAO inhibitors or within 14 days of MAOI discontinuation due to risk of hypertensive crisis and serotonin syndrome 2, 1
• Avoid in patients with uncontrolled hypertension, active coronary disease, or significant cardiovascular risk factors 3

Special Populations

• Ensure adequate contraception in women of childbearing potential due to topiramate's teratogenicity risk (orofacial clefts) 1, 4
• Consider monthly pregnancy testing for women of reproductive potential 1
• Monitor serum bicarbonate periodically with long-term use due to topiramate's carbonic anhydrase inhibitor properties 1

Common Pitfalls to Avoid

• Do not confuse this combination with the discontinued "fen-phen" (phentermine-fenfluramine), which carried valvular heart disease risks attributed to fenfluramine, not phentermine 3
• Watch for discontinuation syndrome with shorter-acting SSRIs (particularly paroxetine, but also sertraline and fluvoxamine) if doses are missed 2
• Be aware that one case report documented psychosis with the combination of venlafaxine (an SNRI, not SSRI) and phentermine/topiramate, though causality was unclear 5