While antipsychotics have provided many people with schizophrenia relief from symptoms, nonadherence and treatment discontinuation remain a challenge. For some, nonadherence stems from the lack of efficacy of antipsychotics. For others, nonadherence is due to a range of side effects from antipsychotic therapy, with some rare effects even classified as potentially life-threatening.1

Antipsychotics can have a broad range of neurological, behavioral, and peripheral system effects as a result of their actions on a variety of neurotransmitter receptors. Extrapyramidal side effects (EPS), including dystonia, akathisia, parkinsonism, and tardive dyskinesia, are well-recognized adverse effects of first-generation antipsychotics. With second-generation (atypical) antipsychotics, EPS are less frequent. However, as symptomatic targets for antipsychotics broaden, there is a higher potential for adverse effects reaching a larger group of patients.2

In addition, antipsychotics can affect the cardiovascular, pulmonary, and metabolic systems. Patients on certain antipsychotics may experience sedation or insomnia and sexual or reproductive system dysfunction that can impair quality of life. An increased incidence of pneumonia can occur with certain antipsychotics. Lastly, patients may experience weight gain, dyslipidemia, or diabetes, which has been related to metabolic syndrome and even a higher risk for heart disease or stroke.1,3

Every medication comes with the risk of side effects, but for people with schizophrenia, the potential adverse effects associated with antipsychotics may be daunting. Given the long list of potential side effects and the challenges with illness insight in some patients, it is no wonder that patients may hesitate to start these medications, let alone continue taking them if they start to experience clinically relevant side effects.  

Finding the right antipsychotic for each patient is key. Shared decision-making between the patient and provider is essential. This approach considers factors such as anticipated risks, benefits, and the patient’s individual values and preferences in selecting a treatment strategy.4 Managing side effects when they occur by lowering the dose, switching therapies, or treating with a nonpharmacological or pharmacological intervention can help patients stay adherent to their therapy.1

For some patients, one reason for nonadherence may be the limited efficacy of some antipsychotics.5 This could be due to many reasons, including the fact that some antipsychotics primarily treat the positive symptoms of schizophrenia, with less effect on negative and cognitive symptoms.2 Additionally, approximately 40% of patients may experience treatment-resistant schizophrenia.6 In this context, it can be challenging for providers to determine whether a patient is nonadherent or experiencing a poor treatment response.7 It is essential to evaluate each patient thoroughly to avoid discontinuing treatment, switching treatment, or increasing dosage too soon due to suspected nonadherence.8 Finding the ideal treatment for a patient may require trial and error.    

Schizophrenia is still an all too often debilitating and chronic disease that can greatly affect quality of life and overall functioning. Medication side effects can make this disease even more difficult for patients. Nonadherence is strongly associated with poor clinical outcomes, a greater risk for and duration of hospitalization, and psychotic relapse.8

Patients with treatment-resistant schizophrenia often have additional challenges with everyday living and are more likely to live in healthcare facilities.9 Choosing antipsychotics with the least side effects first, avoiding side effects that matter to patients the most, and monitoring and managing adverse effects as well as ensuring that patients are on the right treatment plan for them, which may involve long-acting injectable antipsychotic options,10 can help them stay adherent to their medication and obtain the greatest possible benefit from treatment.    

References:  

  1. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018;17(3):341-356. doi:10.1002/wps.20567  
  2. Weston-Green K. Antipsychotic drug development: from historical evidence to fresh perspectives. Front Psychiatry. 2022;13:903156. doi:10.3389/fpsyt.2022.903156  
  3. Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757-777. doi:10.2147/TCRM.S117321  
  4. Pillinger T, Howes OD, Correll CU, et al. Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development. Lancet Psychiatry. 2023;10(11):860-876. doi:10.1016/S2215-0366(23)00262-6
  5. Lähteenvuo M, Tiihonen J. Antipsychotic polypharmacy for the management of schizophrenia: evidence and recommendations. Drugs. 2021;81(11):1273-1284. doi:10.1007/s40265-021-01556-4  
  6. Diniz E, Fonseca L, Rocha D, et al. Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates. Braz J Psychiatry. 2023;45(5):448-458. doi:10.47626/1516-4446-2023-3126.
  7. Howes OD, McCutcheon R, Agid O, et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216-229. doi:10.1176/appi.ajp.2016.16050503.
  8. El Abdellati K, De Picker L, Morrens M. Antipsychotic treatment failure: a systematic review on risk factors and interventions for treatment adherence in psychosis. Front Neurosci. 2020;14:531763. doi:10.3389/fnins.2020.531763  
  9. Nucifora FC Jr, Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131:104257. doi:10.1016/j.nbd.2018.08.016  
  10. Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies. Lancet Psychiatry. 2021;8(5):387-404. doi:10.1016/S2215-0366(21)00039-0