Approach
Management should be viewed as lifelong and involves the establishment of a stable maintenance antipsychotic regimen and psychosocial interventions, supported by a comprehensive follow-up plan. Nonadherence can be an important problem, because many patients have diminished insight into their condition.[40]
Most mental illnesses, including schizoaffective disorder, are associated with increased frequency of medical illnesses, with on average 15- to 20-year reduction in life expectancy. Managing the adverse effects of medications is crucial, as many of these further increase the risk of medical illness.
Early intervention services, with tailored psychosocial and pharmacologic interventions, are associated with superior outcomes compared with treatment as usual.[25][26][27]
Pharmacotherapy
There are very few medications approved for use specifically in schizoaffective disorder. However, in clinical practice, most of the medications used for schizophrenia and mood disorder are also used in schizoaffective disorder.
For patients initially diagnosed with schizoaffective disorder, treatment should begin with a low dose of an antipsychotic agent, with particular attention to the development of adverse effects. Standard of care is to start patients on an atypical (second-generation) antipsychotic medication.[41] There is no guideline as to which medication out of this class should be started first; this decision is made considering the adverse-effect profile and other factors (e.g., sedation).[42]
For patients with established illness, review previous treatments, including dose, duration, and response for each agent.
In patients with an extensive history of nonadherence, long-acting intramuscular agents need to be considered. Oral efficacy and tolerability should be established before switching to a long-acting intramuscular agent.[43]
If two different antipsychotic medications fail to be effective, a trial of clozapine can be considered. Patients need to be prescribed the minimum dose that controls their symptoms, and adequate follow-up is necessary to determine if medication needs to be adjusted or if any new adverse effects develop.
Mood stabilizer medications and antidepressants play an important role in combination with antipsychotic medications.
Management of an acute psychotic episode
An acute psychotic episode may occur in 1 of 3 settings:
The first psychotic episode
Psychotic decompensation
Resistance to antipsychotic medication.
It is important that the patient be in a safe and predictable environment. Hospitalization is often needed, especially in cases of violence, decreased control of behavior, poor judgment, or suicidality.
If the acute episode is also the first presentation, the patient needs to be established on antipsychotic medication. Such patients are usually naïve to antipsychotic agents and should be started on low doses with subsequent titration.
If the acute episode was due to psychotic decompensation or to antipsychotic resistance, the medication dose often needs to be increased or a new antipsychotic medication started. If there has been a good response to a specific agent in the past and the acute episode is a direct result of nonadherence, the patient's treatment can be titrated to the dose that was previously effective.
In cases of extreme agitation and violence, parenteral medication (rapid tranquilization) may be used if de-escalation techniques and oral benzodiazepines have failed, and only if absolutely necessary after weighing up the risks and benefits. Protocols for rapid tranquilization vary. Intramuscular lorazepam alone is often used and is recommended in some guidelines.[33] Haloperidol is used less often as it is associated with a risk of extrapyramidal side effects (e.g., dystonia). Cochrane systematic reviews have found that adding promethazine to haloperidol is supported by some evidence from randomized trials, but adding a benzodiazepine to other drugs is not supported by evidence, and increases the potential for adverse effects.[44][45] There is a lack of evidence to support the use of alternative antipsychotic drugs, including oral risperidone, in rapid tranquilization.[44][46] The American Psychiatric Association guideline on the treatment of patients with schizophrenia also warns that while emergency administration of antipsychotic medication may be useful in individuals with acute agitation, it can also reduce tolerability and may contribute to a perception that premature dose increases are needed.[32]
Pharmacologic management of a first episode
For patients with a new diagnosis, antipsychotics, other than clozapine and olanzapine (which have a problematic side-effect profile), are recommended as first-line treatment.[47] Antipsychotics should be started at a low dose and titrated gradually according to response.[47] Particular attention should be paid to adverse effects of the medication. In a systematic review of second-generation antipsychotic trials, there was no evidence that acute use of antipsychotics increased mortality in the short term, though risk may be increased in vulnerable populations such as patients with dementia.[48]
Mood stabilizers can be added to antipsychotic medication for manic or mixed symptoms associated with the illness, and antidepressants can be added to antipsychotic medication for depression symptoms associated with the illness.
Pharmacologic management of multiple-episode disorder
Antipsychotics
For patients with an acute psychotic exacerbation of schizoaffective disorder, the first line of treatment should be an antipsychotic agent other than clozapine.[47] The benefits of atypical antipsychotics, in terms of decreased risk for extrapyramidal adverse effects and tardive dyskinesia, need to be balanced on an individual basis against an increased risk for weight gain and metabolic syndrome that is reported with atypical antipsychotics (e.g., olanzapine).[41] The selection is made after considering clinical presentation, patient preference and prior adherence, immediate and longer-term adverse effects of the medications, response to previous interventions, and possible financial costs to the patient and family.[47] Antipsychotics differ substantially in side effects, and there are small but robust differences seen in efficacy.[49]
Olanzapine might be somewhat superior to other atypical antipsychotics; however, this small increase in superiority needs to be carefully weighed against its higher risk for significant weight gain and metabolic syndrome when compared with all other antipsychotics (except clozapine).[50]
In patients with established illness, information on previous treatments, dose, duration of treatment, and response to each particular agent should be gathered. In patients with an extensive history of nonadherence, long-acting intramuscular formulations should be considered. Oral efficacy and tolerability should be established before switching to a long-acting intramuscular agent.[43]
Patients should be given the minimum dose that controls their symptoms, with adequate follow-up for possible medication adjustments and monitoring of adverse effects. Medication should be continued indefinitely, but titrated, switched to another agent, or discontinued if adverse effects are intolerable. There is no correlation between the dose and therapeutic effect, but the risk of extrapyramidal signs (e.g., akathisia, parkinsonism, and dystonia) increases with dose.
For patients who do not achieve a satisfactory treatment response with antipsychotics, augmentation with lithium may improve the clinical response.[51] In cases of treatment resistance, where patients fail to respond to at least two adequate trials of two different antipsychotics, clozapine may be recommended. A trial of clozapine should last a minimum of 8 weeks.[47]
In people with treatment-responsive, multi-episode schizoaffective disorder who are experiencing an acute exacerbation of their illness, the minimum recommended length of treatment trial is 2 weeks, with an upper limit of 6 weeks to observe optimal response. For maintenance therapy, continuous treatment is recommended. Intermittent, targeted treatment may increase the risk for symptom exacerbation and relapse, and it is not recommended.[47]
Mood stabilizers
Can be added to antipsychotic medication for manic or mixed symptoms associated with the illness, and antidepressants can be added to antipsychotic medication for depression symptoms associated with the illness. Antidepressants should be prescribed conservatively, mostly during the course of a depressive episode, in order to avoid a precipitation of a manic or mixed episode. Lithium, carbamazepine, divalproex sodium, or lamotrigine can be used to control mood swings. Serum drug levels should be monitored - therapeutic levels vary between laboratories.
In the US, standard practice is that valproate and its analogs are only prescribed for the treatment of manic episodes associated with bipolar disorder or schizoaffective disorder during pregnancy if other alternative medications are not acceptable or not effective. In 2018, the European Medicines Agency (EMA) recommended that valproate and its analogs are contraindicated in bipolar disorder during pregnancy due to the risk of congenital malformations and developmental problems in the infant/child.[52] The EMA did not comment specifically on use of valproate during pregnancy in schizoaffective disorder, but it is reasonable to extrapolate that this is also contraindicated. In both Europe and the US, valproate and its analogs must not be used in female patients of childbearing potential unless there is a pregnancy prevention program in place and certain conditions are met.[52]
Anxiety
Patients with symptoms of anxiety may benefit from the addition of an anxiolytic, such as a benzodiazepine, for a short period.[53] Studies have failed to demonstrate that buspirone is consistently effective against panic attacks.[54][55]
Psychosocial interventions and psychotherapy
Patients should be engaged in person-centered treatment that includes both evidence-based pharmacologic and nonpharmacologic treatment.[32] Individuals with first-episode psychosis should be treated in a coordinated specialty care program that involves a collaborative shared decision-making model, including family education, case management, and work or education support. These programs have been associated with lower mortality, lower rates of relapse, and improved quality of life and functioning. Barriers involve limited availability and program funding.[32]
Psychosocial interventions are key components of long-term management. The Patient Outcomes Research Team (PORT) guidelines recommend the following psychosocial interventions: assertive community treatment, supported employment, skills training, cognitive behavioral therapy (CBT), token economy interventions, and family-based services.[47]
[ 
]
CBT for psychosis (CBTp), cognitive remediation, psychoeducation, and supportive therapy have been shown to be effective and should be started early in treatment.[32][47][56] CBTp is more efficacious in decreasing positive symptoms, and social skill training is efficacious in decreasing negative symptoms.[57][58]
A minimum duration of 16 CBTp sessions is recommended.[32][59] However, studies suggest that treatment benefits may no longer be significant after 6 months.
Other psychosocial interventions include the following.
Assertive community treatment: may be beneficial in situations where there is poor engagement with services, such as homelessness and legal issues such as incarceration.[32]
Supported employment services: more effective than other vocational approaches in improving competitive work.[60]
Psychoeducation: patient education about their diagnosis, medication, and self-management fosters insight, adherence, and improved health-related quality of life.[61] [
]
Psychoeducation is typically integrated in clinical practice and can be particularly helpful in patients with schizoaffective disorder in instilling hope and providing reassurance, support, and empowerment. There is moderate-strength evidence showing reduction in relapse rates and low-strength evidence for improvements in global functioning.[32]Supportive psychotherapy: commonly used in practice, but is less evidence-based than other psychosocial interventions (e.g., coordinated specialty care, CBTp, psychoeducation).[32] A reality-based testing and present-centered focus aims to help patients cope with their illness, learn adaptive skills, and improve self-esteem.[32]
Intensive case management: may reduce hospitalization and increase retention in care compared with standard care. It globally improves social functioning, although its effect on mental state and quality of life remains unclear.[62] [
]
Cognitive remediation: a form of rehabilitation that focuses on improving cognitive deficits seen in schizophrenia/schizoaffective disorder with the goal of enhancing functioning and quality of life.[32] Programs of cognitive remediation may focus on cognitive processes such as attention, memory, executive function, social cognition, and meta-cognition. Cognitive remediation has been shown to improve cognition, symptoms, and function and may be more robust when used adjunctively with other forms of psychosocial rehabilitation.[63][64][65]
Cognitive enhancement treatment: early intervention with cognitive enhancement treatment, when compared with enriched supportive therapy, has been shown to improve social cognition, cognitive style, social adjustment, and symptomatology, with sustained improvements for up to 2 years.[66][67]
Other interventions
Suicide prevention includes monitoring depressive symptoms and risk factors for suicide. See Suicide risk management.
Case management should be implemented early in the illness process. Family issues need to be monitored and addressed early because family interventions are very useful in relapse prevention.
Evidence suggests electroconvulsive therapy (ECT) is beneficial in patients with schizophrenia, particularly in patients with catatonia or significant suicide risk.[32] ECT is also effective for refractory major mood symptoms and may be considered for treatment-refractory schizoaffective disorder in conjunction with antipsychotic therapy.
There are no clear studies demonstrating superiority of specific antipsychotics as augmentation with ECT. In studies of patients with schizophrenia, symptoms and rates of remission improved with clozapine plus ECT treatment compared with clozapine alone.[32][68] Some evidence suggests antipsychotics other than clozapine may also be beneficial.[32]
Other medications may need to be adjusted before starting ECT as some (e.g., benzodiazepines, lithium) can affect the treatment.[69] Consult a specialist for guidance.
Health maintenance
Most psychiatric illnesses, including schizoaffective disorder, are associated with increased frequency of medical illnesses and with a 15- to 20-year reduction in life expectancy. Managing the adverse effects of medications is crucial, because many of these agents further increase the risk of medical illness. Health maintenance is, therefore, targeted to these adverse effects.
Neurologic adverse effects: patients should be monitored for the development of extrapyramidal signs (akathisia, parkinsonism, and dystonia) and tardive dyskinesia. These are particularly common in patients taking typical antipsychotic medications. The Abnormal Involuntary Movement Scale is very useful for this purpose, even though it is not specific for tardive dyskinesia, and should be routinely utilized.[70]
Metabolic abnormalities: the use of atypical antipsychotic medications requires careful monitoring for metabolic adverse effects. Weight should be monitored at every visit. An increase of one point in the BMI (unless the BMI <18.5) should prompt consideration of an alternative agent. Waist circumference needs to be monitored. A baseline fasting glucose should be obtained for all patients before starting a new antipsychotic agent. Patients with significant risk factors should have fasting glucose at 4 months, and then yearly. If weight gain is present, fasting glucose needs to be done every 4 months. The lipid panel should be checked when the patients are on antipsychotic medications and be rechecked every 2 years if low-density lipoprotein (LDL) is normal, or every 6 months if LDL is >130 mg/dL. Any abnormality should be appropriately managed with lipid-lowering and antidiabetic therapy as required.[35]
Excessive prolactin: antipsychotic medication with higher dopamine blockade, such as haloperidol, fluphenazine, and risperidone, can cause increased prolactin with galactorrhea, gynecomastia, and amenorrhea.[71] Clinicians should remain alert for these effects and decrease the dose or change medications if they occur.
Cardiac abnormalities: QT prolongation, T-wave flattening, and torsades de pointes have been reported with antipsychotic use. A baseline ECG is unnecessary in most cases, but special attention is justified in patients with known conduction abnormalities. Some agents (e.g., ziprasidone) are prone to cause QT prolongation, and their use requires ECG monitoring.
WBC: agranulocytosis has been reported with most antipsychotic medications, but regular WBC monitoring is required only in patients taking clozapine (every week for the first 6 months and every 2 weeks indefinitely after that).
Postural hypotension: this may occur in any patient and is usually transitory in the first hours or days of treatment. For older patients this adverse effect can be persistent and dose-limiting. Precautionary measures include patient education to assume the upright position slowly.
Anticholinergic adverse effects: symptoms can be divided into peripheral (e.g., dry mouth, constipation, blurred vision, urinary retention) and central (e.g., delirium). Patients usually develop tolerance to adverse effects such as dry mouth. Rinsing with water or chewing sugarless gum helps. For blurred vision, a temporary reduction of the medication dose may be indicated. If acute urinary retention or delirium occurs, medication needs to be discontinued.
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