Second-generation antipsychotics and patient functioning

The treatment and management of schizophrenia may include a variety of different modalities, such as medication and psychotherapy, rehabilitation to enhance adaptive skills and providing environmental support, for instance supported housing and employment.¹ However, Professor Tandon said interventions may be associated with some adverse impacts, such as side effects with antipsychotic medications.² The net impact of the intervention is determined by the extent it is able to decrease the disease burden, weighed against the addition of any treatment burden,¹ thus forming the rationale for the choice of second-generation or atypical antipsychotic medication over first-generation antipsychotics for schizophrenia.¹

Atypical antipsychotic medications have different side effects

Professor Tandon said second-generation antipsychotic medications are similarly effective as first-generation antipsychotics against psychotic symptoms, with the exception of clozapine, which is more effective in some patients.^1,3,4 However, each medication has a different side effect profile and their tolerability may differ between individual patients.¹

Treatment side effects can impose a significant overall burden on patients, with one study finding that 61% of study participants with psychosis reported impairment in their daily life as a result of medication side effects, and 30% reporting moderate or severe impairment.⁵ If not addressed early, side effects can cause long-term distress and contribute to chronic health complications.⁶ A consequence of experiencing side effects is medication non-adherence.^7,8

The patient’s view of antipsychotic side effects

A web-based survey of 435 adult patients with schizophrenia aimed to gain a deeper understanding of the functional and quality of life impacts of antipsychotic medication side effects, from the patients’ perspective using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF).² 

Looking specifically at the side effects patients experienced, the study authors grouped them into sedating side effects, which included ‘feeling drugged or like a zombie’ and being sleepy during the day; activating side effects, including difficulty sleeping, restlessness and shaky hand or arms; and other side effects, such as weight gain or problems enjoying sex.² Sedating side effects (p<0.05) had the most frequent impact on functioning, followed by activating side effects (not statistically significant).² Professor Tandon said an important aspect of the study was that it presented the patient’s experience of side effects and impact on function, not the clinician’s.

Do clinicians and patients have the same treatment priorities?

Treatment efficacy on symptoms and tolerability are high priorities for clinicians when choosing a treatment;⁹ however, patients’ priorities may differ. For example, in young patients recently diagnosed with schizophrenia, aspects of functioning like the ability to think clearly, family relationships and experiencing fuller emotions are highly prioritised.¹⁰ Professor Tandon said it’s really important that clinicians think of the impact on patients’ lives of the treatments they are prescribing. As all medications have side effects, it is necessary to balance those parameters with the patient’s experience of side effects and their perceived impact on functioning.²

Treatment outcomes in schizophrenia: incorporating evidence into practice

Schizophrenia is a heterogeneous illness with respect to symptoms, course and treatment,¹¹ so there is no one treatment approach that works for everyone. Professor Citrome said selecting a suitable treatment for each patient requires the use of evidence-based medicine,¹² combining the relevant clinical evidence with clinical judgement and patients’ treatment preferences.¹² NNT and NNH are concepts related to the benefit–risk profile of an intervention, with NNT denoting the number of patients who would need to be treated with a given intervention for 1 of them to experience the desired positive outcome.¹³ Conversely, NNH is the number needed to treat before 1 patient experiences a given negative outcome.¹³ Professor Citrome said NNT and NNH allow indirect comparisons to be made between different antipsychotic medications.¹⁴

Using risk factors to inform treatment choice

A 2015 study found that patients with specific adverse event risk factors are often treated with medications that are associated with that same adverse event; extrapyramidal symptoms, obesity and sedation being frequent examples.¹⁵ Professor Citrome said these suboptimal choices are made because drug treatment choices become limited when a patient has multiple risk factors.¹⁵ To help guide treatment choice, clinicians can segment their patients by risk profile.¹⁵ Having determined the risk segment or segments, medication can be selected on the basis of it being least likely to cause an adverse event within that risk segment.¹⁵

Patients’ values and preferences 

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial found that for five antipsychotic drugs reported, “Patient’s decision to discontinue treatment” was a more frequent reason why medication was discontinued compared to lack of efficacy or tolerability (p values not reported).¹⁶ Professor Citrome said this means clinicians need to meet patients ‘where they are’ and think about their motivation for taking medicine, their experience living with the illness and what they are looking for in terms of treatment outcome. 

Key Points

• The impact of antipsychotic side effects on patient-centred outcomes has not been well documented²
• A recent survey² highlights the importance of capturing patients’ perspectives when evaluating antipsychotic treatment success
• There is a need for individualised treatment to enable symptom control without inducing side effects that impair patient functioning and quality of life^2,15
• Evidence-based medicine can help inform optimal treatment decisions, but it requires clinical judgment and integration with a patient’s values and preferences¹²
• Understanding the relevant scientific evidence requires the evaluation of effect size; for which NNT and NNH can be useful¹⁴