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Initiate pharmacotherapy at the dose recommended by the manufacturer (for most patients) and titrate to a maximally tolerable dose (Table 3).
Patients who are worried about side effects can be started at
half-doses or less.
Lower doses and more gradual titration may be needed for patients with co-occurring anxiety disorders and for elderly patients.
Evidence suggests that higher SSRI doses produce a somewhat higher response rate and somewhat greater magnitude of symptom relief.
Some patients may benefit from even higher doses than those shown in the last column of Table 3. Monitor such patients closely for side effects including serotonin syndrome.
There is no apparent relationship between OCD treatment outcome and plasma levels of SRIs.
Starting Dose and Incremental Dose (mg/day)a
Usual Target Dose (mg/day)
Usual Maximum Dose (mg/day)
Occasionally Prescribed Maximum Dose (mg/day)b
aSome patients may need to start at half this dose or less to minimize undesired side effects such as nausea or to accommodate anxiety about taking medications.
bThese doses are sometimes used for rapid metabolizers or for patients with no or mild side effects and inadequate therapeutic response after 8 weeks or more at the usual maximum dose.
cCombined plasma levels of clomipramine plus desmethylclomipramine 12 hours after the dose should be kept below 500 ng/mL to minimize risk of seizures and cardiac conduction delay.
dSertraline, alone among the selective serotonin reuptake inhibitors, is better absorbed with food.
Continue pharmacotherapy for 8–12 weeks, including 4–6 weeks at a maximally tolerable dose.
Most patients will not experience substantial improvement until
4–6 weeks after starting medication, and some who will ultimately respond will experience little improvement for as many as
Patients who have not responded to a known effective dose after 10–12 weeks may respond at higher doses.
Some clinicians prefer to titrate doses more rapidly (in weekly increments to the maximum recommended dose if this is comfortably tolerated) rather than waiting for 1–2 months before each dose increment.
Manage medication side effects.
A first step is to consider if lowering the drug dose may alleviate the side effect without loss of therapeutic effect.
Clomipramine is likely to induce anticholinergic effects, although these typically diminish over time. Side effects may include delayed urination, weight gain and sedation, orthostatic hypotension and postural dizziness, and cardiac arrhythmias and seizures. Starting at a dose of 25 mg/day or less will increase early tolerability.
Common side effects of SSRIs and management strategies are described in Table 4. Sexual side effects may affect one-third or more of patients taking SSRIs.
Carefully monitor patients taking SSRIs for suicidal thoughts and suicidal or other self-harming behaviors, particularly during the early phases of treatment and after dosage increases.
A discontinuation syndrome consisting of dizziness, nausea/vomiting, headache, and lethargy but also agitation, insomnia, myoclonic jerks, and paresthesias may occur if medication is suddenly stopped. The syndrome may occur with any SRI but is most often seen with paroxetine or the serotonin-norepinephrine reuptake inhibitor venlafaxine. A slow taper over several weeks or more will minimize the likelihood of discontinuation symptoms.
Fatigue or sleepiness
Add modest doses of modafinil.
Start with low doses.
Advise that mild queasiness or nausea will usually disappear within 1–2 weeks at a constant dose.
Recommend taking the medication in the morning.
Recommend sleep hygiene measures.
Add a sleep-promoting agent.
Sexual side effects
Reduce the dose to that which is minimally effective.
Wait for the symptom to remit.
Recommend a once-weekly, one-day "drug holiday" before engaging in sexual activity (not effective for fluoxetine).
Switch to another SSRI.
Add a counteracting pharmacological agent (e.g., bupropion).
Add a low-dose anticholinergic agent such as benztropine.
Add clonidine, cyproheptadine, or mirtazapine.
Provide CBT at least once weekly for 13–20 weeks.
The literature and expert opinion suggest that 13–20 weekly
sessions with daily homework (or 3 weeks of weekday daily CBT) is an adequate trial for most patients. More severely ill patients may require longer treatment and/or more frequent sessions.
Consider booster sessions for more severely ill patients, patients who have relapsed in the past, and those who show signs of early relapse.
The psychiatrist may conduct the CBT or refer the patient for this or another adjunctive psychotherapy.
Monitor the patient's psychiatric status in follow-up visits.
The frequency of follow-up visits may vary from a few days to
2 weeks. The indicated frequency will depend on the severity of the patient's symptoms, the complexities introduced by co-occurring conditions, whether suicidal ideation is present, and the likelihood of troublesome side effects.
The patient should be encouraged to telephone between visits if medication questions arise. If telephone calls become reassurance rituals, work with the patient and the patient's family to limit call frequency, using treatment as for any other ritual.