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Central Nervous System

Non-adherence in patients with schizophrenia: An issue of impaired insight

  • Nonadherence to antipsychotic medication remains a major challenge for the effective treatment of schizophrenia patients1.
  • Impaired insight – patient’s lack of awareness or understanding of illness plus medication – is a critical factor for non-adherence to treatment2,3
  • Emerging interventions like second-generation antipsychotics and psychotherapies like cognitive behavior therapies (CBT) and metacognitive training can play important role in improving patients’ insight into schizophrenia4,5

Schizophrenia is a serious mental illness that affects approximately 24 million people or 1 in 300 individuals (0.32%) worldwide. The onset of Schizophrenia is mostly associated with late adolescence and is observed to occur earlier among men than among women6. It impairs the person’s ability to think, feel and behave. Schizophrenia causes psychosis characterized by severe imparity in the way reality is perceived. This causes significant changes in behavior, sometimes leading to delusions, hallucinations, and the experience of influence, control, or passivity. Additionally, individuals with schizophrenia also rate low on cognitive skills such as memory, attention, and problem-solving6.

Management of schizophrenia – treatment options and importance of adherence

Schizophrenia treatment primarily involves supporting individuals to manage their symptoms, improve day-to-day functioning, and achieve personal life goals, like education, career, and fulfilling relationships. Antipsychotic medications form the backbone of schizophrenia treatment and are supported with psychological treatments like cognitive behavioral therapy, behavioral skills training, and cognitive remediation interventions7.

Adherence to antipsychotic medication is critical for the treatment of patients with schizophrenia. Non-adherence can lead to exacerbation of illness, increased risk of relapse, and less responsiveness to subsequent treatments. Other consequences of non-adherence include re-hospitalization, poor quality of life or psycho-social outcomes, increased comorbid medical conditions, wastage of healthcare resources, and increased rates of suicide1. However, treatment adherence is a major clinical challenge in schizophrenia, with approximately 50% of patients being non-adherent or suboptimally adherent1.

Factors for non-adherence to antipsychotic medication

Key determinants for antipsychotic medication non-adherence are:

  • Medication side effects: Dizziness, fatigue, sedation, lethargy, and sleepiness are the most frequently reported side effects that contribute to medication non-adherence to antipsychotic medications1. Weight gain is another medication-related adverse effect that contributes to patients’ perception of their medication, often leading to non-adherence1.
  • Medication duration: Long treatment duration (6–12 months and longer) and long-term medication prescriptions have also been associated with psychotropic medication non-adherence1.
  • Treatment complexity: Using multiple and frequent doses along with multiple drug combinations due to the complicated drug regimen that is associated with anti-psychotics is also a significant barrier to adherence1.
  • Co-morbidity: Psychotropic medication adherence is reportedly sub-optimal in patients suffering from other co-morbidities, especially in the presence of other mental illnesses like obsessive-compulsive disorders, recovering from mania-hypomania, and personality disorders1.
  • Impaired insight about illness and medication: Patients’ lack of insight (awareness) about their illness and medication is also an important factor associated with psychotropic medication non-adherence. Likewise, misunderstanding and perception about the treatment consequences have been associated with enhanced non-adherence1.
  • Medication cost: Financial burden owing to the longer duration of antipsychotic therapy is a major challenge in reducing adherence to these medications1.
  • Socio-demographic factors:Patient’s employment, education, and age are among the other considerable factors attributing to non-adherence. The social stigma associated with mental disorders further fuels this non-adherent behavior1.
  • Substance abuse/misuse: Use of psychostimulants (eg cigarette smoking) and psycho-depressants, and concurrent alcohol dependency are reported to be associated with psychotropic medication non-adherence1.

Role of patients’ impaired insight in schizophrenia

Impaired insight poses a major challenge in schizophrenia patients’ treatment due to its potential to jeopardize therapeutic engagement and medication adherence. Poor insight or unawareness/denial of illness has been commonly observed in schizophrenia and is recognized as a risk factor for poor outcomes. Approximately, 50 – 80% of patients with schizophrenia are reported to have impaired insight into their illness2,3. Schizophrenia patients who do not perceive themselves as ill, are less inclined to adhere to treatment. They are less likely to appreciate the benefits of medication, thereby are at higher risk of discontinuing treatments, leading to an increase in the risk of relapse.

Key analysis from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study reported that schizophrenia patients with higher insight impairment are less likely to adhere to their medication8,9. Moreover, patients with moderate-to-severe insight impairment were non-adherence earlier in the treatment as compared to those patients that had minimal or no impairment9. These results indicate a strong correlation between impaired insight and nonadherence to antipsychotic medication.

Interventions to positively modulate patient insights

Interventions that enhance patients’ insight into their illness early during treatment have the potential to improve medication adherence in patients with schizophrenia8. Development of a positive attitude towards medication during the early phases of treatment is critical, as early acceptance or rejection of medication predicts adherence throughout treatment10,11.

Despite its importance, inadequate progress has been made in developing an effective intervention to improve adherence in patients with schizophrenia. Novel treatment approaches – pharmacological and psychological – explored to enhance patient’s insights and in turn, adherence to schizophrenia treatment are discussed below:

  • Second-generation antipsychotics: Although second-generation antipsychotics like clozapine, olanzapine, risperidone, aripiprazole, etc. have been suggested to be associated with improvements in insight in schizophrenia association, was not observed when the analysis was controlled for other clinical factors. These findings indicate that second-generation antipsychotic effects on impaired insight were mediated by overall improvement in symptoms4.
  • Psychological therapies: Psychological therapies have also been investigated for their impact on insight in schizophrenia patients. These include cognitive behavioral therapy (CBT), psycho-education, adherence therapy, social skills training, and metacognitive training5. Studies have demonstrated small to moderate effects of psychological interventions on insight, although individual approaches differ in overall effectiveness5. Among them, CBT and metacognitive training have received the utmost attention for their impact on insight.
    • Cognitive Behavioral Therapy: CBT, specifically adapted for patients with psychosis, is associated with improvements in insight12. It complements medication management and is effective in managing symptoms, improving insight, enhancing compliance, and reducing aggression in schizophrenia patients13.
    • Metacognitive training: Metacognitive training is an emerging therapy for psychotic illness. Specifically, metacognitive reflection insight therapy (MERIT) addresses insight in schizophrenia. It assists patients in increasing their understanding of their distorted mental processes or their self-appraisal abilities14. MERIT is reported to be specifically effective for schizophrenia patients with poor insight. A study assessing MERIT in patients with first-episode psychosis and poor clinical insight reported that patients who received 6 months of MERIT had statistically significant improvements in insight without any increases in hopelessness or emotional distress, relative to those patients who had standard meetings with therapists15.

Conclusions:

In conclusion, addressing issues of impaired insight in schizophrenia patients, corresponding to a lack of understanding of the disease state and purpose of medications, is key to improving medication non-adherence and the overall clinical outcome of the patients. This would require a holistic treatment approach, using a combination of pharmacological therapies alongside psychological therapy.

“Schizophrenia cannot be understood without understanding despair”.- By R.D. Laing, Psychiatrist

References

1.    Semahegn A, Torpey K, Manu A, Assefa N, Tesfaye G, Ankomah A. Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis. Syst Rev. Jan 16 2020;9(1):17. doi:10.1186/s13643-020-1274-3

2.    Vohs JL, George S, Leonhardt BL, Lysaker PH. An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments. Expert Rev Neurother. Oct 2016;16(10):1193-204. doi:10.1080/14737175.2016.1199275

3.    Lysaker PH, Vohs J, Hillis JD, et al. Poor insight into schizophrenia: contributing factors, consequences and emerging treatment approaches. Expert Rev Neurother. Jul 2013;13(7):785-93. doi:10.1586/14737175.2013.811150

4.    Mattila T, Koeter M, Wohlfarth T, et al. The impact of second generation antipsychotics on insight in schizophrenia: Results from 14 randomized, placebo controlled trials. Eur Neuropsychopharmacol. Jan 2017;27(1):82-86. doi:10.1016/j.euroneuro.2016.10.004

5.    Sauve G, Lavigne KM, Pochiet G, Brodeur MB, Lepage M. Efficacy of psychological interventions targeting cognitive biases in schizophrenia: A systematic review and meta-analysis. Clin Psychol Rev. Jun 2020;78:101854. doi:10.1016/j.cpr.2020.101854

6.    WHO. Schizophrenia Fact Sheet. Accessed 10 January 2022, https://www.who.int/news-room/fact-sheets/detail/schizophrenia

7.    Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P T. Sep 2014;39(9):638-45.

8.    Kim J, Ozzoude M, Nakajima S, et al. Insight and medication adherence in schizophrenia: An analysis of the CATIE trial. Neuropharmacology. May 15 2020;168:107634. doi:10.1016/j.neuropharm.2019.05.011

9.    Lysaker PH, Weiden PJ, Sun X, O’Sullivan AK, McEvoy JP. Impaired insight in schizophrenia: impact on patient-reported and physician-reported outcome measures in a randomized controlled trial. BMC Psychiatry. Aug 28 2022;22(1):574. doi:10.1186/s12888-022-04190-w

10.  Mohamed S, Rosenheck R, McEvoy J, Swartz M, Stroup S, Lieberman JA. Cross-sectional and longitudinal relationships between insight and attitudes toward medication and clinical outcomes in chronic schizophrenia. Schizophr Bull. Mar 2009;35(2):336-46. doi:10.1093/schbul/sbn067

11.  Rabinovitch M, Bechard-Evans L, Schmitz N, Joober R, Malla A. Early predictors of nonadherence to antipsychotic therapy in first-episode psychosis. Can J Psychiatry. Jan 2009;54(1):28-35. doi:10.1177/070674370905400106

12.  Li ZJ, Guo ZH, Wang N, et al. Cognitive-behavioural therapy for patients with schizophrenia: a multicentre randomized controlled trial in Beijing, China. Psychol Med. Jul 2015;45(9):1893-905. doi:10.1017/S0033291714002992

13.  Rathod S, Phiri P, Kingdon D. Cognitive behavioral therapy for schizophrenia. Psychiatr Clin North Am. Sep 2010;33(3):527-36. doi:10.1016/j.psc.2010.04.009

14.  Moritz S, Klein JP, Lysaker PH, Mehl S. Metacognitive and cognitive-behavioral interventions for psychosis: new developments. Dialogues Clin Neurosci. Sep 2019;21(3):309-317. doi:10.31887/DCNS.2019.21.3/smoritz

15.  Vohs JL, Leonhardt BL, James AV, et al. Metacognitive Reflection and Insight Therapy for Early Psychosis: A preliminary study of a novel integrative psychotherapy. Schizophr Res. May 2018;195:428-433. doi:10.1016/j.schres.2017.10.041