Under‐utilized opportunities to optimize medication management in long‐term treatment of schizophrenia
Authors: Matti Isohanni, Jouko Miettunen, Erika Jääskeläinen, Jani Moilanen, Anja Hulkko, Sanna Huhtaniska
Journal: World Psychiatry (2018)

Millions of people use antipsychotic medications and thousands of clinicians prescribe and monitor this treatment every day worldwide. In their review, Correll et al1 highlight key issues regarding the long-term use of these medications. Herein we further discuss such issues, based on additional literature and data from Finnish cohort studies2-6. Three cornerstones in the long-term medication of schizophrenia are evidence-based use of antipsychotics, adjuvant psychosocial therapies, and optimal medication management. Correll et al review key findings and problems with the first and second of these cornerstones. Could good medication management alleviate these problems? Medication management is defined as a process aimed to facilitate safe and effective use of medications and optimize therapeutic outcomes7. Multiple models of medication management have been put forward2, 7, but no systematic reviews, meta-analyses or universal treatment recommendations are available. Incomplete evidence on the content and cost-effectiveness of optimal antipsychotic medication management must be balanced with the development of organization-specific practices. Proper approaches to medication management include shared decision making in prescription, follow-up, and monitoring at regular intervals7. In addition, careful documentation of response, continuity, and coordination of care should be ensured by a well-trained multidisciplinary team. However, in clinical practice, medication management is often suboptimal6, 7. Schizophrenia patients with impaired cognition or motivation and/or poor financial resources have an elevated risk of inadequate medication management. Important principles include avoiding maximal doses and polypharmacy, in favor of using the lowest possible effective and tolerated dose, choosing an antipsychotic associated with minimal side effects, and using adjuvant psychosocial interventions. For instance, maximal psychosocial and medication management interventions reduced the mean dose of antipsychotics from 370 to 160 mg/day as chlorpromazine equivalents in a Finnish therapeutic community ward of patients with acute psychosis2. However, currently used doses may sometimes be too high, as a reflection of insufficient or missing psychosocial therapies or poor medication management. Current clinical practice guidelines are non-specific with respect to optimal doses, dose tapering, low-dose maintenance and discontinuation of antipsychotics. Guidelines do not specify how to go about tapering (i.e., at what point in the clinical course of illness, over what time period). This uncertainty may induce clinicians to set the bar high in dose reduction or withdrawal owing to potential risks. In practice, changes in antipsychotic dosing are done by testing and monitoring clinical response in the individual patient. This testing presupposes good medication management. A vital long-term aim in medication management is to minimize unwanted drug effects such as tardive dyskinesia, weight gain or metabolic disturbances. Adverse effects attributable to chronic antipsychotic exposure are often cumulative over a period of years. A meta-analysis found associations between long-term antipsychotic use and brain volume changes8. Antipsychotics may also impact on brain plasticity and cognitive functioning5. Brain effects appear to be dose-dependent: high cumulative doses are related to brain alterations3 and cognitive decline5. Paying attention to side effects, and adjusting and trying to find the lowest effective and tolerated dose could also decrease the dramatically high prevalence of medication non-adherence in schizophrenia9. As stressed by Correll et al, there are major methodological challenges when studying long-term antipsychotic use. Scientific evidence on dose reduction or medication discontinuation is primarily based on observational studies, which are subject to potential biases. Randomized controlled trials (RCTs) can help determine only the short-term efficacy and adverse effects. Such trials tend to be reductionistic when analyzing the complex interactions between brain, environment, drug effects and care. RCTs tend not to detect different subgroup effect sizes and long-term advantages and harms. Non-adherence and attrition are also alarming problems in medication studies. Effective medication management may reduce them. In the Northern Finland Birth Cohort 1966 Study3-6, we initially had a low participation rate of patients during the 9-year follow-up (44%). With maximal management efforts, including home visits, the participation rate increased in subsequent follow-ups (67%). There are no major breakthroughs in the efficacy of antipsychotic treatment in sight. Current antipsychotics diminish illness expression, but do not restore lost complex brain functions. Many patients (and clinicians) do not utilize these medications optimally, even though their efficacy is quite high. Improving medication management and thus the risk-benefit ratio of antipsychotics is a realistic goal in the near future. In summary, current care guidelines and practice standards advise us on how to use antipsychotics, most definitively at the group level and during the first years of illness. Long-term use and medication management skills and services are inadequately studied. It is important to learn what not to do when aiming at long-term improvement in medication management. Do not leave the patient alone with the medication. Do not forget the intellectual power of and need for psychoeducation and social support to patients and relatives. Do not remain silent or uninformed on patients' drug attitudes, treatment adherence, and negative experiences. Do not use only your brain, but also your heart and empathy. Do not assume (even though you are a well-trained and experienced clinician) sole responsibility for long-term care and medication, but involve psychiatric and somatic teams, ensure continuity of care and organizational support. The efficacy and risk-benefit balance of antipsychotics are not fixed. They can be improved through optimal medication management, particularly after the first years of the disease. Matti Isohanni1, Jouko Miettunen1, 2, Erika Jääskeläinen1-3, Jani Moilanen1, Anja Hulkko1, 2, Sanna Huhtaniska1, 2 1Center for Life Course Health Research, University of Oulu, Oulu, Finland; 2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; 3Department of Psychiatry, Oulu University Hospital, Oulu, Finland