Antipsychotic treatment adherence improves functional outcome for bipolar I disorder and schizophrenia

A good functional outcome — improved cognition; ability to work, study, live independently, participate in recreational activities and interpersonal relationships; and improved sexual function — is a key objective for individuals with bipolar I disorder and for those with schizophrenia. It depends on symptom control and relapse prevention, and these in turn depend on treatment adherence, which is best achieved using long-acting injectable (LAI) rather than oral antipsychotics, explained experts from Austria, USA, Canada and Spain, in a symposium at CINP 2018.  Relapses lead to a progressive deterioration in function, and in schizophrenia are associated with adverse psychosocial consequences. It is therefore particularly important to prevent these complications early in the course of the illness to optimize the potential for better functioning over the long-term.

Many factors contribute to functional outcomes for patients with bipolar I disorder or schizophrenia, including adherence to medication, said Wolfgang Fleischhacker, Professor and Managing Director of the Department of Psychiatry and Psychotherapy, Innsbruck University Clinics, Innsbruck, Austria.

Relapses in bipolar I disorder and poor functional outcomes are associated with nonadherence

Previous manic episodes are significantly associated with poor function

Functional impairments in patients with bipolar I disorder affect cognition, ability to work, study and live independently and participate in recreational activities, and interpersonal and sexual relationships, 1 said Eduard Vieta, Professor of Psychiatry, University of Barcelona, Catalonia, Spain — and they are significantly associated with previous manic episodes.2

In addition, a significant negative correlation exists between adherence and occupational impairment,3 and adherent patients with therapeutic levels of medications indicated for the treatment of bipolar disorder are less likely to be hospitalized than those who are partially adherent with sub-therapeutic levels.4

Relapse rates in bipolar I disorder range from 40–85% over 1–5 years,5 and are associated with nonadherence to treatment6 (40–50% of patients are nonadherent7) and progressive pathological changes in the brain,8 added Joseph R. Calabrese, Director of the Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.8

40–50% of patients do not adhere to their treatment

Professor Vieta highlighted that treatment with a LAI antipsychotic improves adherence for patients with bipolar I disorder and has been shown to:

  • lower relapse rates9,10
  • significantly lower the risk of psychiatric re-hospitalization compared with oral antipsychotic therapy11
  • lower the risk of recurrence of any mood episode over 52 weeks by approximately 50% compared with placebo12
  • maintain improvements in function over 52 weeks — particularly improved interpersonal relationships and cognitive and occupational function13

LAI antipsychotic therapy improves treatment adherence

A 52-week safety and efficacy study comparing treatment with a LAI antipsychotic with placebo in patients presenting in the manic phase of bipolar I disorder14 was described by Professor Calabrese. Compared with placebo, those treated with a LAI antipsychotic had:

  • significantly delayed the time to recurrence of any mood episode (p<0.0001)14
  • lowered the risk of recurrence of any mood episode over 52 weeks by approximately 50%14
  • significantly decreased the proportion of manic mood recurrences14
  • significantly increased the median time to all-cause discontinuation (345 days vs 170 days)14
  • decreased the risk of discontinuation over 52 weeks by almost 40%14

In terms of tolerability, no clinically meaningful changes were seen in treatment-emergent adverse events or weight gain.14

Relapse prevention early in the course of schizophrenia improves functional outcome

Antipsychotic therapy helps in preventing relapse in schizophrenia

Relapse prevention is particularly important early in the course of schizophrenia to prevent psychosocial consequences in terms of education or work opportunities, said Wolfgang Fleischhacker, Professor and Managing Director of the Department of Psychiatry and Psychotherapy, Innsbruck University Clinics in Innsbruck, Austria.

A systematic review and meta-analysis of 65 randomized controlled trials involving 6493 patients with schizophrenia has demonstrated that after 12 months, 64% of patients on placebo relapse compared with 27% of patients on antipsychotic therapy.15

Furthermore, compared with oral antipsychotics, LAI antipsychotic therapy:

  • lowers the risk of re-hospitalization by 22% (32% in newly diagnosed patients)16  
  • lowers the risk of death over 15–20 years by approximately 10%17
  • lowers the risk of discontinuation of treatment (p<0.05)18
  • improves symptoms measured by the Positive and Negative Syndrome Scale (p<0.05)18

Psychiatrists underestimate patient acceptability of LAI antipsychotic therapy

Early initiation of treatment with a LAI antipsychotic could be beneficial for both patients with schizophrenia and their carers, and might possibly change the course of the illness, said Ofer Agid, professor of psychiatry, Schizophrenia Program, Centre for Addiction and Mental Health in Toronto, Canada.

However, despite the evidence that early and effective treatment favorably alters outcomes, treatment with a LAI antipsychotic is generally not considered for first-episode patients.19 Psychiatrists underestimate patient acceptability of LAIs20 and tend to reserve it for patients with established nonadherence, poor insight, and multiple relapses, explained Professor Agid.

Doctor–patient communication is critical for patient acceptance of treatment and can benefit from a shared decision-making approach informed by the clinical evidence, Professor Agid said. Addressing the goals that are of value to an individual patient and involving the patient are key to treatment success.

This symposium was sponsored by H. Lundbeck A/S.

References
  1. Rosa et al. Clin Pract Epidemiol Ment Health 2007;3:5.
  2. Sanchez-Moreno et al. Acta Psychiatr Scand 2018;10.1111/acps.12894.
  3. Rosa et al. Bipolar Disord 2009;11:401–409.
  4. Scott & Pope. Am J Psychiatry 2002;159:1927–1929.
  5. Gitlin & Miklowitz. J Affect Disord 2017;209:147–154.
  6. Hajda et al. Neuropsychiatr Dis Treat 2016;12:1561–1570.
  7. Chakrabarti. World J Metaanal 2017;5(4):103–123.
  8. Dodd et al. Prog Neuropsychopharmacol Biol Psychiatry 2013;42:135–145.
  9. Kishi et al. Int J Neuropsychopharmacol 2016;19(9):1–10.
  10. Vieta et al. Eur Neuropsychopharmacol 2012;22(11):825–835.
  11. Lähteenvuo et al. JAMA Psychiatry 2018;75(4):347–355.
  12. Calabrese et al. J Clin Psychiatry 2017;78(3):324–331.
  13. Madera et al. Poster presented at the 30th annual US Psychiatric & Mental Health Congress, 16–19 September 2017, New Orleans, LA, USA.
  14. Calabrese et al. J Clin Psychiatry 2017;78(3):324–331.
  15. Leucht et al. Lancet 2012;379(9831):2063–2071.
  16. Tiihonen et al. JAMA Psychiatry 2017;74:686–693.
  17. Taipale et al. Schizophr Res 2017;10.1016/j.schres.2017.12.010.
  18. Fleischhacker et al. Br J Psychiatry 2014;205:135–144.
  19. Agid et al. Expert Opin Pharmacother 2010;11(14):2301–2317.
  20. Cahling et al. BJPsych Bull 2017;41(5):254–259.
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