Schizoaffective disorder is a perplexing mental illness that has both features of schizophrenia and features of a mood disorder. The coupling of symptoms from these divergent conditions makes diagnosing and treating schizoaffective patients difficult.
The first step in evaluation is to obtain a complete medical history, keeping in mind the diagnostic criteria for schizoaffective disorder.
Several scales are available for rating the severity of disease (eg, PANSS). The Questionnaire is useful for investigating alcohol consumption in patients with schizoaffective disorder.
The next step is to perform a complete mental status examination (MSE), physical examination, and neurologic examination to assist with the evaluation and rule out other disease processes. The MSE typically includes assessment of the following:
See Presentation for more detail.
The diagnosis of schizoaffective disorder is made when the patient has features of both schizophrenia and a mood disorder but does not strictly meet diagnostic criteria for either alone. Ongoing reevaluation over the course of the illness is important for confirming the diagnosis.
Laboratory studies that may be performed include the following:
Psychological testing (eg, Structured Clinical Interview for Axis I DSM-IV Disorders [SCID-1]) is warranted to assist with diagnosis.
Additional studies that may be helpful include the following:
See Workup for more detail.
Management principles include the following:
Selection of medications to treat schizoaffective disorder depends on whether the depressive or manic subtype is present. In the depressive subtype, combinations of antidepressants plus an antipsychotic are used. In the manic subtype, combinations of mood stabilizers plus an antipsychotic are used.
Antipsychotics used to treat schizoaffective disorder include the following:
Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred to the other classes of antidepressants in this setting. They include the following:
Mood stabilizers used in this setting are as follows:
See Treatment and Medication for more detail.
Schizoaffective disorder can be defined according to either Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) , criteria (see below) or International Classification of Diseases, Tenth Revision (ICD-10) coding. It is a perplexing mental illness that has both features of schizophrenia (eg, hallucinations, delusions, and distorted thinking) and features of a mood disorder (eg, depression or mania). The coupling of symptoms from these divergent spectrums makes diagnosing and treating schizoaffective patients difficult.
The diagnosis is made when the patient has features of both schizophrenia and a mood disorder but does not strictly meet diagnostic criteria for either illness alone. Unfortunately, it is often difficult to determine whether a patient has 1 of the 2 distinct illnesses (schizophrenia or a mood disorder), a combination of the 2 illnesses (schizophrenia with a mood disorder), or perhaps even a different illness entirely.
An accurate diagnosis is made when the patient meets criteria for major depressive disorder or mania while also meeting the criteria for schizophrenia. Moreover, the patient must have psychosis for at least 2 weeks without a mood disorder.
To diagnosis schizoaffective disorder, one must complete the patient’s history, review medical and psychiatric records, and, if possible, obtain information from family members.[1, 2]
Men with schizoaffective disorder tend to exhibit antisocial personality traits. The age of onset is later for women than for men, and because of limited research in this area, the exact etiology and epidemiology are unclear. Patients with schizoaffective disorder are thought to have a better prognosis than patients with schizophrenia do. Treatment consists of both pharmacotherapy and psychotherapy.
The specific DSM-5 criteria for schizoaffective disorder are as follows :
Subtypes are defined as bipolar type (if a manic episode is part of the presentation, though major depressive episodes may also occur) and depressive type (if only major depressive episodes are part of the presentation). The presence or absence of catatonia is specified.
Various course specifiers are used, though only if the disorder has been present for at least 1 year and if they do not contradict diagnostic course criteria. These specifiers include the following:
Finally, the current severity of the disorder is specified by evaluating the primary symptoms of psychosis and rating their severity on a 5-point scale ranging from 0 (not present) to 4 (present and severe).
The exact pathophysiology of schizoaffective disorder is unknown but may involve neurotransmitter imbalances in the brain. Abnormalities of the neurotransmitters serotonin, norepinephrine, and dopamine could play a role in this disorder. Reduced hippocampal volumes, thalamic abnormalities, and white-matter abnormalities have been noted in patients with schizoaffective disorder.[6, 7, 8]
Although the cause of schizoaffective disorder is unknown, it may be similar to that of schizophrenia. To date, no specific genetic markers have been identified. In utero exposure to viruses, malnutrition, or even birth complications may play a role. More research is needed to fully elucidate the causes of schizoaffective disorder.
The frequency of schizoaffective disorder worldwide is difficult to determine, because the diagnostic criteria have changed over the past few years. A Finnish study estimated the lifetime prevalence of schizoaffective disorder to be about 0.32%. A French review cited a range of 0.5-0.8%. These numbers are only estimates; no studies have been performed.
Young people with schizoaffective disorder tend to have the bipolar subtype, whereas older people tend to have the depressive subtype. Overall, the disorder affects more women than men, probably in part because more women have the depressive subtype as opposed to the bipolar subtype. Men with schizoaffective disorder tend to exhibit antisocial traits and behavior in contrast to other personality traits. In addition, the age of onset is later for women than for men. No race-based differences in frequency have been observed.
The prognosis for patients with schizoaffective disorder is thought to lie between that of patients with schizophrenia and that of patients with a mood disorder. That is, the prognosis is better than that of schizophrenia alone but worse than that of a mood disorder alone.
Individuals with the bipolar subtype are thought to have a prognosis similar to those with bipolar type I, whereas the prognosis of people with the depressive subtype is thought to be similar to that of people with schizophrenia. Overall, determination of the prognosis is difficult.[11, 12, 13, 14]
The overall incidence of suicide is estimated to be about 10%. The incidence of suicide attempts varies among different ethnic and social groups.[15, 16] White individuals have a higher rate of suicide than do African Americans. People who immigrated to a country have higher suicide rates than people born in that country do. Women attempt suicide more than men do, but men complete suicide more often.
A poor prognosis in patients with schizoaffective disorder is generally associated with a poor premorbid history, an insidious onset, an absence of precipitating factors, a predominant psychosis, negative symptoms, an early onset, an unremitting course, or having a family member with schizophrenia.
Patients should be educated about the following:
Family education should involve reduction of expressed emotions, criticism, hostility, or overprotection of the patient; such reduction may lead to decreases in relapse rates.
Useful online patient information is available from the following sites:
The first step in evaluation is to obtain a complete medical history, keeping in mind the diagnostic criteria for schizoaffective disorder. (See Background.)
Several scales are available for rating the severity of disease in patients with schizophrenia or schizoaffective disorder. These scales include those for positive and negative symptoms (eg, the Positive and Negative Symptom Scale for Schizophrenia [PANSS] ) and many for depression and bipolar rating (eg, the Hamilton depression scale and the Young mania scale). Such tools can be used for baseline and outcome measurements and may be useful in assessing the patient’s progress.
The CAGE (cut down, annoyed, guilty, eye opener) Questionnaire is useful for investigating alcohol consumption in patients with schizoaffective disorder.
The next step is to perform a complete mental status examination (MSE), physical examination, and neurologic examination to assist with the evaluation and rule out other disease processes.
Although the MSE varies from patient to patient, there are several items that are commonly assessed in most patients with possible schizoaffective disorder. Because of the variability of the presentation of this disorder, any or all symptoms of schizophrenia, bipolar disorder, or major depressive disorder may manifest, depending on the presenting subtype, as follows:
It is essential to inquire about suicidal ideation at each visit; individuals with schizoaffective disorder have a significant lifetime risk for suicide. In addition, it is important to inquire about past acts of self-harm or violence. To help determine suicidal ideation or intent, ask the following types of questions: “Do you have any thoughts of wanting to harm or kill yourself?” and “Do you have any thoughts that you would be better off dead?”
If patient replies in the positive to any of these questions, inquire about specific plans, suicide notes, family history (anniversary reaction), and impulse control. Also, ask how the patient views suicide to determine if a suicidal gesture or act is ego-syntonic or ego-dystonic. Next, determine if the patient will contract for safety.
It is also important to inquire about homicidal ideation or intent during each patient interview. To help determine homicidal ideation or intent, ask the following types of questions: “Do you have any thoughts of wanting to hurt anyone?” and “Do you have any feelings or thoughts that you wish someone were dead?” If the patient replies in the positive to any of these questions, ask if he or she has any specific plans to injure someone and how he or she plans to control these feelings if they occur again.
Workup may include selected laboratory tests, psychological testing, diagnostic imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI]), or electroencephalography (EEG).
Laboratory studies that may be performed include the following:
DSM-IV Disorders [SCID-1]) is warranted to assist with diagnosis. If the patient's neurologic findings are abnormal, performing CT or MRI to rule out any suspected intracranial pathology may be appropriate. EEG should be performed if indications are present.
Histologic findings include decreased amounts of cortical gray matter and increased fluid-filled spaces.
Treatment consists of both pharmacotherapy and psychotherapy. Written informed consent must be obtained before pharmacologic therapy is started. To maximize benefits and adherence to treatment, the treatment plan must be individualized for each patient. Consultation with a neurologist to rule out neurologic disease is appropriate.
Patients who are suicidal, homicidal, or gravely disabled should be admitted to an inpatient psychiatric unit. Inpatient treatment is mandatory for patients who are dangerous to themselves or others and for patients who cannot take care of themselves. If patients with schizoaffective disorder represent a danger to self or others or are gravely disabled and are unwilling to seek help on a formal voluntary basis, they may have to be committed for further evaluation and treatment.
Transfer to a medical surgical hospital should be considered if it appears necessary, as should transfer to a residential or group home. Familiarity with local mental health laws is essential.
Smoking cessation and noncompliance with medications are special concerns. It is important to monitor treatment adherence for medications and other therapeutic activities.[37, 38]
No specific diet is recommended for patients with schizoaffective disorder. Activity should be restricted if patients represent a danger to themselves or others or if they are gravely disabled; otherwise, patients should be encouraged to continue their normal routines and strengthen their social skills whenever possible.
Several medications are used to treat schizoaffective disorder. Agent selection depends on whether the depressive or manic subtype is present. Early treatment with medication along with good premorbid function often improves outcomes.[39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57]
In the depressive subtype, combinations of antidepressants (eg, sertraline or fluoxetine) plus an antipsychotic (eg, haloperidol, risperidone, olanzapine, aripiprazole, or ziprasidone[61, 59] ) are used. In refractory cases, clozapine has been used as an antipsychotic agent. In the manic subtype, combinations of mood stabilizers (eg, lithium, carbamazepine, divalproex) plus an antipsychotic are used.
Other antipsychotics that have been used in this setting include paliperidone (the active metabolite of risperidone),[63, 64, 65, 66] iloperidone, quetiapine, and asenapine.
Quetiapine is sometimes prescribed at higher than approved doses for patients with schizophrenia or schizoaffective disorder. Honer et al did not find dosages higher than 800 mg/day to offer any advantage beyond what was achievable with the approved dosage range.
The use of ziprasidone dosages higher than the standard maximum of 160 mg/day has also been proposed. Goff et al, in a study comparing 160 mg/day and 320 mg/day dosages in individuals with schizophrenia or schizoaffective disorder whose symptoms did not resolve after a minimum of 3 weeks of ziprasidone 160 mg/day, found that the higher dosage did not yield a sustained increase in serum concentrations or symptomatic improvement in comparison with the standard dosage.
Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred to the other classes of antidepressants. Because their adverse-effect profiles are less prominent than the profiles of other drugs, improved compliance is promoted. SSRIs do not have the cardiac dysrhythmia risk associated with tricyclic antidepressants. This risk is especially pertinent in overdose, and suicide risk must always be considered when one treats a child or adolescent with a mood disorder.
Physicians are advised to be aware of the following information and to use appropriate caution when they consider treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory stating that most SSRIs are not suitable for use by persons younger than 18 years for treatment of depressive illness. After review, the MHRA decided that the risks to pediatric patients outweighed the benefits of treatment with SSRIs, except in the case of fluoxetine, which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (both ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Noncompliance with medications is a complication of therapy. If noncompliance with medications is an issue, one may seek a court order to force the patient to take medications (eg, in lieu of rehospitalization), which may help increase medication compliance.
Patients who have schizoaffective disorder can greatly benefit from psychotherapy, as well as from psychoeducational programs.
They should receive therapy that involves their families, develops their social skills, and focuses on cognitive rehabilitation. Expressed emotions must be reduced in all areas of a patient’s life, including stress-reduction techniques employed to prevent relapse and possible rehospitalization. Psychotherapies should include supportive therapy and assertive community therapy in addition to individual and group forms of therapy and rehabilitation programs.
Treatment includes education about the disorder and its treatment, family assistance in compliance with medications and appointments, and maintenance of structured daily activities (eg, a schedule of daily events) for the patient.
Family involvement is needed in the treatment of this particular disorder. Family education is particularly important in this disorder secondary to the various mood and psychotic states. Families need information regarding the patient’s mediations and the dynamic nature of this illness.
For further information, families can contact the National Alliance on Mental Illness (NAMI) or Self-Help Association Regarding Emotions (SHARE; 1-800-832-8032).
When an inpatient who has schizoaffective disorder makes the transition to being an outpatient, stressing the importance of medication compliance is crucial.
Patients with schizoaffective disorder often lack judgment and insight into their illness. They commonly refuse to continue the medications started in the hospital after they are discharged. When patients begin to feel better as a result of their medications, they may think that they no longer need to take them; such thinking leads to the discontinuance of medication and typically results in a return to the hospital within the next several weeks or so. Noncompliance can also be due to adverse effects of the medication, such as sedation and weight gain.
If possible, once-daily or long-acting medications (eg, decanoate injections) should be selected to facilitate patient compliance. In addition, the issue of compliance should be addressed with a family member. In every case, all of the risks, benefits, and adverse effects of each medication, as well as alternatives to the medication, should be discussed with the patient and family.
Several medications are used to treat schizoaffective disorder. Agent selection depends on whether the depressive or the manic subtype is present. Early treatment with medication, along with good premorbid function, often improves outcomes.
In the depressive subtype, combinations of antidepressants (eg, sertraline or fluoxetine) plus an antipsychotic (eg, haloperidol, risperidone, olanzapine, aripiprazole, or ziprasidone) are used. In refractory cases, clozapine has been used as an antipsychotic agent. In the manic subtype, combinations of mood stabilizers (eg, lithium, carbamazepine, and valproic acid) plus an antipsychotic are used.
Clinical Context: Haloperidol is used for managing psychosis, as well as motor and vocal tics in children and adults. The mechanism of action is not clearly established, but the drug exerts a selective effect on the central nervous system (CNS) by competitively blocking postsynaptic dopamine D2 receptors in the mesolimbic dopaminergic system; increases in dopamine turnover are responsible for the tranquilizing effect. With subchronic therapy, depolarization blockade and D2 postsynaptic blockade are responsible for antipsychotic action.
Clinical Context: Risperidone is a selective monoaminergic antagonist that binds to dopamine D2 receptors with a 20 times lower affinity than it binds to serotonin type 2 (5-HT2) receptors. It also binds to alpha1-adrenergic receptors, with lower affinity to H1-histaminergic and alpha2-adrenergic receptors. It improves negative symptoms of psychosis and decreases occurrence of extrapyramidal effects. Risperidone is also available in a long-acting intramuscular (IM) formulation.
Clinical Context: Paliperidone is a major metabolite of risperidone. It improves negative symptoms of psychoses and reduces incidence of EPS. It has high affinity for serotonin type 2 (5-HT2) receptors and binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2 receptors. Antagonism of alpha1-adrenergic, alpha2-adrenergic, and histaminergic receptors is also observed. It has moderate affinity for serotonin type 1 (5-HT1C, 5-HT1D, 5-HT1A) receptors and has weak affinity for dopamine D1 receptors. No affinity for muscarinic, beta1-adrenergic, and beta2-adrenergic receptors has been observed. The IM dosage form (Invega Sustenna) is indicated for schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants.
Clinical Context: Olanzapine is an atypical antipsychotic with a broad pharmacologic profile across receptor systems (eg, serotonin, dopamine, cholinergic muscarinic, alpha-adrenergic, and histamine). Its antipsychotic effect is exerted through antagonism of dopamine and serotonin type 2 receptors. Olanzapine is indicated for treatment of psychosis and bipolar disorder.
Clinical Context: Clozapine has a weak affinity for D1, D2, D3, and D5 receptors and a high affinity for D4 receptors. It also acts as an antagonist at adrenergic, cholinergic, histaminergic, and serotonergic receptors. However, clozapine does not induce catalepsy, nor does it inhibit apomorphine-induced stereotypy. The risk of agranulocytosis limits the use of this agent to patients who are nonresponsive to or intolerant of classic neuroleptic agents.
Clinical Context: Quetiapine is a newer antipsychotic used for long-term management. It may antagonize dopamine and serotonin effects. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.
Clinical Context: Ziprasidone antagonizes D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, and alpha1-adrenergic receptors. It has a moderate antagonistic effect for histamine H1. It moderately inhibits reuptake of serotonin and norepinephrine.
Clinical Context: Aripiprazole improves positive and negative schizophrenic symptoms. Its mechanism of action is unknown but is hypothesized to differ from that of other antipsychotics. Aripiprazole shows high affinity for D2, D3, 5-HT1A, and 5HT2A receptors and moderate affinity for D4, 5HT2C, 5-HT7, alpha1 adrenergic, and H2 receptors and possesses moderate affinity for the serotonin reuptake transporter. It is thought to be a partial D2 and 5-HT1A agonist and a 5-HT2A antagonist. No QTc-interval prolongation is noted in clinical trials.
Clinical Context: Iloperidone is an atypical antipsychotic agent that is indicated for acute treatment of schizophrenia. Its precise mechanism of action is unknown. It antagonizes D2 and 5-HT2 receptors. However, it shows high affinity for 5-HT2A, D2, and D3 receptors and low-to-moderate affinity for D1, D4, H1, 5-HT1A, 5HT6, 5-HT7, and NE alpha1 receptors.
Clinical Context: Paliperidone is the active metabolite of risperidone. Its therapeutic effects consist of mixed central serotonergic and dopaminergic antagonism. Unlike risperidone, paliperidone exhibits 10-fold lower affinity for alpha-2 and 5-HT2A receptors and almost 3- to 5-fold lower affinity for 5-HT1A and 5HT1D, respectively.
Clinical Context: The mechanism of action of asenapine maleate is unknown. Its efficacy is thought to be mediated via combined antagonist activity at D2 and 5-HT2 receptors. The addition of serotonin antagonism to dopamine antagonism may improve the negative symptoms of psychoses and may reduce the incidence of extrapyramidal adverse effects when compared with typical antipsychotics. It is indicated for treatment of schizophrenia and bipolar disorder.
Antipsychotic agents ameliorate psychosis and aggressive behavior.
Clinical Context: Lithium is indicated to treat bipolar disorder. The specific mechanism of action is unknown, but the drug alters sodium transport in nerve and muscle cells and influences reuptake of serotonin, norepinephrine, or both at cell membranes.
Clinical experiences have shown that patients with bipolar disorder have fewer episodes of mania and depression when treated with mood-stabilizing drugs. These medications serve to stabilize the patient’s mood, as the name implies. They also can dampen extremes of mania or depression.
Lithium is the drug commonly used for prophylaxis and treatment of manic episodes. A recent study suggests that lithium may also have a neuroprotective role.
Clinical Context: Fluoxetine is an SSRI used to treat impulse-control problems or underlying illness. It selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine.
Clinical Context: Sertraline is an SSRI used to treat impulse-control problems or underlying illness. It selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine.
Clinical Context: Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance, the dosing should be adjusted so as to maintain the patient on the lowest effective dosage, and the patient should be periodically reassessed to determine the need for continued treatment.
Clinical Context: Fluvoxamine enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than TCAs do. Fluvoxamine has been shown to reduce repetitive thoughts, maladaptive behaviors, and aggression and to increase social relatedness and language use.
Clinical Context: Citalopram enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. No head-to-head comparisons of SSRIs have been done; however, on the basis of metabolism and adverse effects, citalopram is considered the SSRI of choice for patients with head injury.
Clinical Context: Escitalopram is an SSRI and an S-enantiomer of citalopram. It is used for the treatment of depression. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS, resulting from inhibition of CNS neuronal reuptake of serotonin. The onset of depression relief may be obtained after 1-2 weeks—sooner than is possible with other antidepressants.
Antidepressants decrease aggression and treat the underlying illness. Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred to the other antidepressant classes. Because the adverse-effect profiles of SSRIs are less prominent than those of other drugs, improved compliance is promoted. SSRIs do not have the cardiac dysrhythmia risk associated with tricyclic antidepressants (TCAs). Dysrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered in treating a child or adolescent with a mood disorder.
Physicians are advised to be aware of the following information and to use appropriate caution when they consider treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory stating that most SSRIs are not suitable for use by persons younger than 18 years for treatment of depressive illness. After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except in the case of fluoxetine, which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality in clinical trials of various antidepressant drugs in pediatric patients. The FDA asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Clinical Context: Valproic acid may increase brain gamma-aminobutyric acid (GABA) levels by inhibiting aminobutyrate aminotransferase. GABA inhibits presynaptic and postsynaptic discharges. In addition to its use as a mood stabilizer, valproic acid is also used for migraine headaches, epilepsy, and mania.
Clinical Context: Oxcarbazepine's pharmacologic activity is primarily from its 10-monohydroxy metabolite (MHD). It may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Its anticonvulsant effect may also be achieved by affecting potassium conductance and high-voltage activated calcium channels.
Drug pharmacokinetics are similar in children older than 8 years and in adults. Children younger than 8 years have a 30-40% increased clearance as compared with older children and adults. Use of oxcarbazepine in children younger than 2 years has not been studied in controlled trials.
Clinical Context: Carbamazepine is indicated to treat epilepsy and trigeminal neuralgia. Research and clinical experience indicate that it is effective in treating manic subtype schizoaffective disorder.
Some anticonvulsants work as mood stabilizers to correct the mood imbalance associated with bipolar disorder.