Schizophrenia Spectrum and Psychotic Disorders

Antipsychotic Switching in Schizophrenia: Immediate vs Gradual Discontinuation

Douglas Strassler
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New Antipsychotics
New Antipsychotics
Both immediate and gradual discontinuation of the current antipsychotic medication are viable treatment options.

Both immediate and gradual discontinuation of the current antipsychotic medication prescribed in a patient with schizophrenia remain equally viable options, a study reported in Schizophrenia Bulletin. However, clinicians should elect an antipsychotic switching strategy that best fits their patient’s needs.1

Researchers at the Schizophrenia Division of the Centre for Addiction and Mental Health in Toronto, Ontario, Canada, compared immediate discontinuation with a gradual antipsychotic tapering approach. Both have risks: Immediate antipsychotic discontinuation has been linked with dopamine supersensitivity syndromes, rebound syndromes, and emergence/exacerbation of symptoms. A gradual tapering approach, however, has been associated with an increased risk of side effects that may be addictive or synergistic in the context of a crossover approach.2-7

Since previous reviews that recommended the gradual switching strategy as a safer method were derived from empirical evidence rather than actual data from clinical trials, the researchers conducted a systematic review and meta-analysis of 9 existing randomized controlled trials examining the two distinct switching patterns in patients with schizophrenia.

The 9 studies involved 1416 patients: 714 for immediate discontinuation, and 702 patients for gradual discontinuation of antipsychotics. All studies represented parallel-group randomized controlled trials (RCTs) with a short duration (ranging from 3 to 12 weeks), and were published in 2000 or later. One study was a double-blind study, the raters were blinded in 3, and the remaining 5 were open-label studies.

No significant differences in any clinical outcomes were found between the two approaches (all Ps>.05).One RCT and 4 arms of the included RCTs failed to demonstrate significant differences in the majority of clinical outcomes between the two strategies, supporting the notion that antipsychotic discontinuation strategies  do not have any substantial clinical impact.8, 9-12

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Additionally, sensitivity analysis including 8 comparisons that used an immediate introduction approach found no significant differences in clinical outcomes between immediate and gradual discontinuation of the current antipsychotic.

Not only did this meta-analysis demonstrate no significant differences between immediate and gradual discontinuation of antipsychotics in schizophrenia, it also undercut the notion that gradual discontinuation is a safer option in clinical practice.

“Gradual discontinuation is frequently observed because of the widely held notion that this method diminishes risk of symptom exacerbation and/or side effects,” the investigators wrote. “However, evidence thus far does not necessarily support this notion.”

“Clinicians are advised to choose an antipsychotic switching strategy according to patient needs,” they said, further adding that “immediate antipsychotic discontinuation may be advantageous both for simplicity and because a stalled cross-titration process in antipsychotic switching could end up in antipsychotic polypharmacy.”

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References

  1. Takeuchi H, Kantor N, Uchida H, Suzuki T. Immediate vs Gradual Discontinuation in Antipsychotic Switching: A Systematic Review and Meta-analysis [published online January 2, 2017]. Schizophrenia Bulletin. doi:10.1093/schbul/sbw171.
  2. Weiden PJ, Aquila R, Dalheim L, Standard JM. Switching antipsychotic medications. J Clin Psychiatry. 1997;58(suppl10):63-72.
  3. Edlinger M, Baumgartner S, Eltanaihi-Furtmüller N, Hummer M, Fleischhacker WW. Switching between second-generation antipsychotics: why and how? CNS Drugs.
  4. 2005;19:27-42. Lambert TJ. Switching antipsychotic therapy: what to expect and clinical strategies for improving therapeutic outcomes. J Clin Psychiatry. 2007;68(suppl 6):10-13.
  5. Cerovecki A, Musil R, Klimke A, et al. Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical recommendations. CNS Drugs. 2013;27:545-572.
  6. Buckley PF. Receptor-binding profiles of antipsychotics:clinical strategies when switching between agents. J Clin Psychiatry. 2007;68(suppl 6):5-9.
  7. Newcomer JW, Weiden PJ, Buchanan RW. Switching antipsychotic medications to reduce adverse event burden in schizophrenia: establishing evidence-based practice. J Clin Psychiatry. 2013;74:1108-1120.
  8. Takeuchi H, Suzuki T, Uchida H, et al. A randomized, openlabel comparison of 2 switching strategies to aripiprazole treatment in patients with schizophrenia: add-on, wait, and tapering of previous antipsychotics versus add-on and simultaneous tapering. J Clin Psychopharmacol. 2008;28:540-543.
  9. Weiden PJ, Simpson GM, Potkin SG, O’Sullivan RL. Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia. J Clin Psychiatry. 2003;64:580-588.
  10. Ganguli R, Brar JS, Mahmoud R, Berry SA, Pandina GJ. Assessment of strategies for switching patients from olanzapine to risperidone: a randomized, open-label, rater-blinded study. BMC Med. 2008;6:17.
  11. Pae C-U, Serretti A, Chiesa A, et al. Immediate versus gradual suspension of previous treatments during switch to aripiprazole: results of a randomized, open label study. Eur Neuropsychopharmacol. 2009;19:562-570. 
  12. Stip E, Zhornitsky S, Potvin S, Tourjman V. Switching from conventional antipsychotics to ziprasidone: a randomized, open-label comparison of regimen strategies. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:
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