Some patients respond to standard doses of SSRIs, however most will need higher doses.12,13 Doses used in trials are listed in the Table. Patients prescribed higher doses should be informed of this and monitored carefully in consultation with a psychiatrist. They should also be warned that response to treatment may be slow and the full effect of their medication may only become evident after 12 weeks. It is usually recommended that SSRIs are increased every two weeks depending on the individual’s response and how they tolerate the medication. Based on response rates in multiple studies,8 an SSRI should be trialled at its maximum dose for at least 12 weeks before concluding it is ineffective.
It is generally recommended that successful treatment with an SSRI should be continued for at least 12 months. Several studies have shown that patients continue to benefit during this period.14,15 A decision to cease successful treatment should be considered carefully as most studies report relapse rates of over 50% within 12 weeks.16 A patient’s life circumstances will need to be evaluated to gauge the risk of relapse and the effect it may have on them. Withdrawing an SSRI should occur slowly, over several months, and preferably with guidance from a psychiatrist when symptoms have been severe.
Combining exposure and response prevention therapy with an SSRI has been shown to be more effective than either alone.16 When a patient does not respond to pharmacotherapy, adding exposure and response prevention therapy is usually recommended. Treament-resistant patients should be referred to a psychiatrist. Deep brain stimulation is used as a treatment of last resort in Australia but is prohibited under the NSW Mental Health Act (2007).
Adverse effects and drug interactions
Prescribers should be aware of the risks associated with prescribing high-dose SSRIs. Patients should be monitored for signs of serotonin syndrome and warned that concomitant St John’s wort or tramadol frequently cause it and should be avoided.
High-dose SSRIs and clomipramine can cause prolonged QT and arrhythmias and so regular ECGs are recommended following a dose escalation. Fluoxetine and paroxetine are both potent inhibitors of cytochrome P450 2D6 and clomipramine inhibits several cytochrome P450 enzymes.