Discontinuing an antidepressant?

Treating ADS. Appropriately recognizing ADS risk and slowly tapering antidepressants as needed usually prevents clinically significant distress associated with discontinuation. For some patients, however, ADS may be particularly severe or prolonged, or may emerge at the end of a slow taper.

Challenging cases may be more likely with paroxetine or venlafaxine—even the extended-release or controlled-release preparations. The elimination half-life of paroxetine is 15 to 20 hours, and the half-lives of venlafaxine and venlafaxine XR are 5 to 11 hours. Desvenlafaxine’s half-life is 11 hours, and product labeling of this enantiomer of racemic venlafaxine notes that discontinuation symptoms have occurred.²⁶ ADS treatment depends on the severity of the reaction and whether or not further antidepressant therapy is necessary.

For mild ADS, reassurance and treatment focused on specific symptoms—such as sedative-hypnotics for insomnia or benzodiazepines for anxiety—may be all that is needed, because ADS tends to gradually resolve over an average of 10 days.²⁷

For more severe ADS, or when ongoing antidepressant therapy is indicated, restarting the recently withdrawn antidepressant at the pre-ADS dosage typically resolves the syndrome within 24 hours. Then employ a slower, more cautious taper when next attempting to discontinue that antidepressant.

Another option. An alternate management strategy is to substitute fluoxetine to suppress ADS associated with shorter half-life SSRIs or SNRIs. Case reports^18,20,28 suggest that fluoxetine, 5 to 20 mg/d, can be used to ameliorate venlafaxine-induced ADS. Fluoxetine can be tried as monotherapy for 1 to 2 weeks and then rapidly tapered or stopped. Others have suggested combination therapy, such as:

• restarting venlafaxine at the pre-ADS dose plus fluoxetine, 20 mg/d
• tapering venlafaxine by 50% every 5 days until stopped
• reducing fluoxetine 1 week later to 10 mg/d for 5 days
• then stopping fluoxetine.²⁸

In general, SSRIs should not be co-administered with SNRIs long-term because of potential additive adverse effects such as serotonin syndrome. Combining fluoxetine with an SNRI such as venlafaxine for the purpose of tapering off venlafaxine and reducing ADS risk probably is safe, however, as long as the fluoxetine dose is low (5 to 20 mg) and SNRI reduction begins immediately, with a plan for complete tapering.

CASE CONTINUED: ECT treatment proceeds

Venlafaxine XR is not restarted to address Mr. J’s suspected ADS because of concerns about potential increased risk for cardiac events (asystole, prolonged bradycardia) during ECT with concomitant venlafaxine use.^29,30 Fluoxetine, which rarely may prolong ECT-induced seizures, is deemed a safer choice and is started immediately at 20 mg/d.

Because of Mr. J’s other symptoms, we prescribe lorazepam, 0.5 mg bid, for anxiety for 2 days; increase aripiprazole to 5 mg bid for agitation; and add zolpidem, 10 mg at bedtime, for insomnia. The following day, Mr. J reports substantial relief from ADS symptoms, including myalgias, paresthesias, and suicidal ideation.^21,23

His second ECT treatment is administered the next day, followed by a successful course of 9 treatments and partial remission of the MDE within 3 weeks. Fluoxetine is reduced to 10 mg/d one week into the ECT series, then discontinued one week later. No signs of emergent ADS are seen at discharge or 2-week outpatient follow-up. Mr. J achieves full remission with maintenance ECT plus bedtime doses of mirtazapine, 30 mg, and aripiprazole, 7.5 mg, across 6 months of follow-up care.

Related resources

• Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry. 2006;67(suppl 4):27-30.
• American Family Physician. Patient handout on antidepressant discontinuation. www.aafp.org/afp/2006/0801/p457.html.
• Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998;44(2):77-87. See appendix for discontinuation-emergent signs and symptoms checklist.

Drug brand names

• Aripiprazole • Abilify
• Bupropion • Wellbutrin
• Clomipramine • Anafranil
• Desvenlafaxine • Pristiq
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Lorazepam • Ativan
• Mirtazapine • Remeron
• Nefazodone • Serzone
• Paroxetine • Paxil
• Sertraline • Zoloft
• Venlafaxine • Effexor
• Venlafaxine extended-release • Effexor XR
• Zolpidem • Ambien

Disclosure

Dr. Muzina reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgment

When Dr. Muzina submitted this article to Current Psychiatry, he was director, Center for Mood Disorders Treatment and Research, Cleveland Clinic Neurological Institute, Cleveland, OH.