Few medications are approved specifically for schizoaffective disorder. In general, medications are chosen to reduce symptoms of psychosis and mood disorder.

Antipsychotic medication is usually required both for acute treatment and the prevention of relapse. There is no single antipsychotic of choice in treating schizoaffective disorder, but atypical antipsychotics should be considered because they have mood-stabilizing activity. Paliperidone is an antipsychotic with FDA approval for the treatment of schizoaffective disorder. Antipsychotics should be used at the minimum dose necessary to control symptoms. Potential side effects include extrapyramidal symptoms, including tremor, muscle stiffness, and restlessness or akathisia. Atypical antipsychotics carry a risk of metabolic syndrome, including weight gain, increased blood sugar, and increased blood cholesterol, so regular monitoring of weight and bloodwork should be carried out. Some atypical antipsychotics, such as ziprasidone and aripiprazole, are associated with less risk than others, such as olanzapine. Medication choice is based on how effectively it reduces symptoms, how few side effects it causes, and cost.

In people with treatment-refractory psychosis, a clozapine trial should be considered. Clozapine is an atypical antipsychotic that is recognized as being particularly effective when other antipsychotic agents have failed. Clozapine should also be considered in people with chronic and persistent suicidal thinking and behaviour, as it has been shown to reduce the risk of suicide in patients with schizoaffective disorder and a history of suicidality. Between 0.5 and 2% of patients taking clozapine may develop a life-threatening complication called agranulocytosis, which is a significant drop in a type of white blood cell. Because of this risk, people taking clozapine must have regular monitoring of blood cell counts.

The management of the bipolar type of schizoaffective disorder is similar to the treatment of bipolar disorder, with the goal of preventing mood episodes and cycling. Lithium or anticonvulsant mood stabilizers such as valproic acid, carbamazepine, and lamotrigine are prescribed in combination with an antipsychotic.

For depression, if an antidepressant is prescribed, "extra attentiveness must be given" by the prescribing clinician due its risk for long-term mood cycle acceleration (that is, inducing more frequent episodes of depression per unit of time) and medication-induced psychosis or mania. For individuals who show emerging psychosis, mania, mixed episode symptoms, or mood cycle acceleration, switching to an antipsychotic plus lithium or lamotrigine is preferable to antidepressants.

For individuals who experience anxiety, anti-anxiety medications can be used, usually on a short-term basis. Benzodiazepines, including lorazepam, clonazepam and diazepam, are types of anti-anxiety medications. Care must be taken when prescribing benzodiazepines due to the risk of the patient developing tolerance and dependence.

The first-line psychiatric treatment for schizophrenia is antipsychotic medication, which can reduce the positive symptoms of psychosis in about 7 to 14 days. Antipsychotics, however, fail to significantly improve the negative symptoms and cognitive dysfunction. In those on antipsychotics, continued use decreases the risk of relapse. There is little evidence regarding effects from their use beyond two or three years. However use of anti-psychotics can lead to dopamine hypersensitivity increasing the risk of symptoms if antipsychotics are stopped.

The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Amisulpride, olanzapine, risperidone, and clozapine may be more effective but are associated with greater side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.

Most people on antipsychotics have side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects, while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol. It remains unclear whether the newer antipsychotics reduce the chances of developing neuroleptic malignant syndrome or tardive dyskinesia, a rare but serious neurological disorder.

For people who are unwilling or unable to take medication regularly, long-acting depot preparations of antipsychotics may be used to achieve control. They reduce the risk of relapse to a greater degree than oral medications. When used in combination with psychosocial interventions, they may improve long-term adherence to treatment. The American Psychiatric Association suggests considering stopping antipsychotics in some people if there are no symptoms for more than a year.

The primary treatment of schizophrenia is antipsychotic medications, often in combination with psychological and social supports. Hospitalization may occur for severe episodes either voluntarily or (if mental health legislation allows it) involuntarily. Long-term hospitalization is uncommon since deinstitutionalization beginning in the 1950s, although it still occurs. Community support services including drop-in centers, visits by members of a community mental health team, supported employment and support groups are common. Some evidence indicates that regular exercise has a positive effect on the physical and mental health of those with schizophrenia.

Electroconvulsive therapy, or ECT, may be considered for patients with schizoaffective disorder experiencing severe depression or severe psychotic symptoms that have not responded to treatment with antipsychotics.

There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants, while bipolar disorder medications can consist of antipsychotics, mood stabilizers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes.

The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (valproate, lithium, or carbamazepine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, or aripiprazole). Although hypomanic episodes may respond to a mood stabilizer alone, full-blown episodes are treated with an atypical antipsychotic (often in conjunction with a mood stabilizer, as these tend to produce the most rapid improvement).

When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy. The likelihood of having a relapse is very high for those who have experienced two or more episodes of mania or depression. While medication for bipolar disorder is important to manage symptoms of mania and depression, studies show relying on medications alone is not the most effective method of treatment. Medication is most effective when used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices.

Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. A systematic review found that long term lithium treatment substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine, which is another anticonvulsant. Clonazepam (Klonopin) is also used. Sometimes atypical antipsychotics are used in combination with the previous mentioned medications as well, including olanzapine (Zyprexa) which helps treat hallucinations or delusions, Asenapine (Saphris, Sycrest), aripiprazole (Abilify), risperidone, ziprasidone, and clozapine which is often used for people who do not respond to lithium or anticonvulsants.

Verapamil, a calcium-channel blocker, is useful in the treatment of hypomania and in those cases where lithium and mood stabilizers are contraindicated or ineffective. Verapamil is effective for both short-term and long-term treatment.

Antidepressant monotherapy is not recommended for the treatment of depression in patients with bipolar disorders I or II, and no benefit has been demonstrated by combining antidepressants with mood stabilizers in these patients.

The treatment of psychosis depends on the specific diagnosis (such as schizophrenia, bipolar disorder or substance intoxication). The first-line psychiatric treatment for many psychotic disorders is antipsychotic medication, which can reduce the positive symptoms of psychosis in about 7 to 14 days.

The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical or atypical antipsychotics are better. Tentative evidence supports that amisulpride, olanzapine, risperidone and clozapine may be more effective for positive symptoms but result in more side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two or three different antipsychotics) in 20% of people. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.

Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol.

The evidence for the effectiveness of early interventions to prevent psychosis appeared inconclusive. Whilst early intervention in those with a psychotic episode might improve short term outcomes, little benefit was seen from these measures after five years. However, there is evidence that cognitive behavioral therapy (CBT) may reduce the risk of becoming psychotic in those at high risk, and in 2014 the UK National Institute for Health and Care Excellence (NICE) recommended preventive CBT for people at risk of psychosis.

Current methods in treating early-onset schizophrenia follow a similar approach to the treatment of adult schizophrenia. Although modes of treatment in this population is largely understudied, the use of antipsychotic medication is commonly the first line of treatment in addressing symptoms. Recent literature has failed to determine if typical or atypical antipsychotics are most effective in reducing symptoms and improving outcomes. When weighing treatment options, it is necessary to consider the adverse effects of various medications used to treat schizophrenia and the potential implications of these effects on development. A 2013 systematic review compared the efficacy of atypical antipsychotics versus typical antipsychotics for adolescents:

Madaan et al. wrote that studies report efficacy of typical neuroleptics such as thioridazine, thiothixene, loxapine and haloperidol, high incidence of side effects such as extrapyramidal symptoms, akathisia, dystonias, sedation, elevated prolactin, tardive dyskinesia.

Various modalities of treatment, including pharmacotherapy, psychotherapy, and various other psychosocial and educational interventions, are used in the treatment of schizophreniform disorder. Pharmacotherapy is the most commonly used treatment modality as psychiatric medications can act quickly to both reduce the severity of symptoms and shorten their duration. The medications used are largely the same as those used to treat schizophrenia, with an atypical antipsychotic as the usual drug of choice. Patients who do not respond to the initial atypical antipsychotic may benefit from

being switched to another atypical antipsychotic, the addition of a mood stabilizer such as lithium or an anticonvulsant, or being switched to a typical antipsychotic.

Treatment of schizophreniform disorder can occur in inpatient, outpatient, and partial hospitalization settings. In selecting the treatment setting, the primary aims are to minimize the psychosocial consequences for the patient and maintain the safety of the patient and others. While the need to quickly stabilize the patient's symptoms almost always exists, consideration of the patient's severity of symptoms, family support, and perceived likelihood of compliance with outpatient treatment can help determine if stabilization can occur in the outpatient setting. Patients who receive inpatient treatment may benefit from a structured intermediate environment, such as a sub-acute unit, step-down unit, partial hospital, or day hospital, during the initial phases of returning to the community.

As improvement progresses during treatment, help with coping skills, problem-solving techniques, psychoeducational approaches, and eventually occupational therapy and vocational assessments are often very helpful for patients and their families. Virtually all types of individual psychotherapy are used in the treatment of schizophreniform disorder, except for insight-oriented therapies as patients often have limited insight as a symptom of their illness.

Since schizophreniform disorder has such rapid onset of severe symptoms, patients are sometimes in denial about their illness, which also would limit the efficacy of insight-oriented therapies. Supportive forms of psychotherapy such as interpersonal psychotherapy, supportive psychotherapy, and cognitive behavior therapy are particularly well suited for the treatment of the disorder. Group psychotherapy is usually not indicated for patients with schizophreniform disorder because they may be distressed by the symptoms of patients with more advanced psychotic disorders.

Treatment consists of supportive care during the acute intoxication phase: maintaining hydration, body temperature, blood pressure, and heart rate at acceptable levels until the drug is sufficiently metabolized to allow vital signs to return to baseline. Typical and atypical antipsychotics have been shown to be helpful in the early stages of treatment. This is followed by abstinence from psychostimulants supported with counseling or medication designed to assist the individual preventing a relapse and the resumption of a psychotic state.

Paranoid schizophrenia is an illness that typically requires lifelong treatment with neuroleptics to allow someone to have a relatively stable and normal lifestyle. In order to be successfully treated, a person with schizophrenia should seek help from family or primary care doctors, psychiatrists, psychotherapists, pharmacists, family members, case workers, psychiatric nurses, or social workers, provided he or she is not unable to do so, due to many people with schizophrenia having the inability to accept their condition. Non-compliance with neuroleptics may also occur if the patient considers the side effects (such as extrapyramidal symptoms) to be more debilitating than the condition itself. The main options that are offered for the treatment of paranoid schizophrenia are the following: neuroleptics, psychotherapy, hospitalization, electroconvulsive therapy, and vocational skills training.

There are many different types of disorders that have similar symptoms to paranoid schizophrenia. There are tests that psychiatrists perform to achieve a correct diagnosis. They include "psychiatric evaluation, in which the doctor or psychiatrist will ask a series of questions about the patient's symptoms, psychiatric history, and family history of mental health problems; medical history and exam, in which the doctor will ask about one's personal and family health history and will also perform a complete physical examination to check for medical issues that could be causing or contributing to the problem; laboratory tests in which the doctor will order simple blood and urine tests can rule out other medical causes of symptoms".

There are side effects associated with antipsychotic medication. Neuroleptics can cause high blood pressure and high cholesterol. Many people who take them exhibit weight gain and have a higher risk of developing diabetes.

For a number of years, scholars debated amongst themselves whether or not antipsychotic drugs had a tendency to increase depression or simply help the patient manage their mental illness. However, conclusive evidence points to antipsychotic drugs actually helping patients with their depression while simultaneously assisting in the suppression of schizophrenic episodes. Specifically risperidone, olanzapine, quetiapine, fluphenazine, haloperidol, and L-sulpiride have done the best in drug trials pertaining to people with schizophrenia. Along with antipsychotic drugs, post-schizophrenic patients may receive antidepressants to actively treat the depression. Drugs are certainly not the only answer, though. At the base of both depression and schizophrenia, social withdrawal is a shared symptom between the two. People suffering from schizophrenia require a strong support system to be healthy, just as is the case with the rest the human population. The opportunity to become a working citizen is another way to ward off depression in patients with schizophrenia, helping them create social ties and a feeling of accomplishment.

According to the Mayo Clinic, it is best to start receiving treatment for paranoid schizophrenia as early as possible and to maintain the treatment throughout life. Continuing treatment will help keep the serious symptoms under control and allow the person to lead a more fulfilling life. This illness is typically unpreventable.

It has a strong hereditary component with a first degree parent or sibling. There is some possibility that there are environmental influences including "prenatal exposure to a viral infection, low oxygen levels during birth (from prolonged labor or premature birth), exposure to a virus during infancy, early parental loss or separation, and verbal, physical or sexual abuse in childhood". Eliminating any of these factors could help reduce an individual's future risk of developing paranoid schizophrenia.

Depressed mood may not require professional treatment, and may be a normal temporary reaction to life events, a symptom of some medical condition, or a side effect of some drugs or medical treatments. A prolonged depressed mood, especially in combination with other symptoms, may lead to a diagnosis of a psychiatric or medical condition which may benefit from treatment. Different sub-divisions of depression have different treatment approaches.

In the United States, it has been estimated that two thirds of people with depression do not actively seek treatment. The World Health Organisation (WHO) has predicted that by 2030, depression will account for the highest level of disability accorded any physical or mental disorder in the world (WHO, 2008).

The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. A recent meta-analysis also indicated that most antidepressants, besides fluoxetine, do not seem to offer a clear advantage for children and adolescents in the acute treatment of major depressive disorder.

Treatment for children suspected of PANDAS is generally the same as the standard treatments for TS and OCD. These include cognitive behavioral therapy and medications to treat OCD such as selective serotonin reuptake inhibitors (SSRIs); and "conventional therapy for tics".

A controlled study (Garvey, Perlmutter, "et al", 1999) of prophylactic antibiotic treatment of 37 children found that penicillin V did not prevent GABHS infections or exacerbation of other symptoms; however, compliance was an issue in this study. A later study (Snider, Lougee, "et al", 2005) found that penicillin and azithromycin decreased infections and symptom exacerbation. The sample size, controls, and methodology of that study were criticized. Murphy, Kurlan and Leckman (2010) say, "The use of prophylactic antibiotics to treat PANDAS has become widespread in the community, although the evidence supporting their use is equivocal. The safety and efficacy of antibiotic therapy for patients meeting the PANDAS criteria needs to be determined in carefully designed trials"; de Oliveira and Pelajo (2009) say that because most studies to date have "methodologic issues, including small sample size, retrospective reports of the baseline year, and lack of an adequate placebo arm ... it is recommended to treat these patients only with conventional therapy".

Evidence is insufficient to determine if tonsillectomy is effective.

An open study of cognitive behavior therapy has aimed to help patients reinterpret their symptoms in a nonthreatening way, leading to an improvement on several standardized measures. A standardized treatment for DPD based on cognitive behavioral principles was published in The Netherlands in 2011.

Primary depersonalization disorder is mostly refractory to current treatments. The disorder lacks effective treatment in part because it has been neglected within the field of psychiatry, which, in turn, is partly because funding has mainly been allocated to the search for cures of other illnesses, like alcoholism. However, recognizing and diagnosing the condition may in itself have therapeutic benefits, considering many patients express their problems as baffling and unique to them, but are in fact: one, recognized and described by psychiatry; and two, those affected by it are not the only individuals to be affected from the condition. A variety of psychotherapeutic techniques have been used to treat depersonalization disorder, such as cognitive behavioral therapy. Clinical pharmacotherapy research continues to explore a number of possible options, including selective serotonin reuptake inhibitors, tricyclic antidepressants, anticonvulsants, and opioid antagonists.

There is no agreed treatment protocol. In most reported cases of ORS the attempted treatment was antidepressants, followed by antipsychotics and various psychotherapies. Little data are available regarding the efficacy of these treatments in ORS, but some suggest that psychotherapy yields the highest rate of response to treatment, and that antidepressants are more efficacious than antipsychotics (response rates 78%, 55% and 33% respectively). According to one review, 43% of cases which showed overall improvement required more than one treatment approach, and in only 31% did the first administered treatment lead to some improvement.

Pharmacotherapies that have been used for ORS include antidepressants, (e.g. selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors), antipsychotics, (e.g. blonanserin, lithium, chlorpromazine), and benzodiazepines. The most common treatment used for ORS is SSRIs. Specific antidepressants that have been used include clomipramine.

Psychotherapies that have been used for ORS include cognitive behavioral therapy, eye movement desensitization and reprocessing.

The use of antipsychotic medication is commonly the first line of treatment; however, the effectiveness after treatment is in question.

L-DOPA is effective against reduced affect display and emotional withdrawal, aloofness from society, apathy.

Psychotherapies that may be helpful in delusional disorder include individual psychotherapy, cognitive-behavioral therapy (CBT), and family therapy.

Treatment is dependent on the underlying cause, whether it is organic or psychological in origin. If depersonalization is a symptom of neurological disease, then diagnosis and treatment of the specific disease is the first approach. Depersonalization can be a cognitive symptom of such diseases as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), neuroborreliosis (Lyme disease), or any other neurological disease affecting the brain. For those suffering from depersonalization with migraine, tricyclic antidepressants are often prescribed.

If depersonalization is a symptom of psychological causes such as developmental trauma, treatment depends on the diagnosis. In case of dissociative identity disorder or DD-NOS as a developmental disorder, in which extreme developmental trauma interferes with formation of a single cohesive identity, treatment requires proper psychotherapy, and—in the case of additional (co-morbid) disorders such as eating disorders—a team of specialists treating such an individual. It can also be a symptom of borderline personality disorder, which can be treated in the long term with proper psychotherapy and psychopharmacology.

The treatment of chronic depersonalization is considered in depersonalization disorder.

A recently completed study at Columbia University in New York City has shown positive effects from transcranial magnetic stimulation (TMS) to treat depersonalization disorder. Currently, however, the FDA has not approved TMS to treat DP.

A 2001 Russian study showed that naloxone, a drug used to reverse the intoxicating effects of opioid drugs, can successfully treat depersonalization disorder. According to the study: "In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."

Prophylactic antibiotic treatments for tics and OCD are experimental and controversial; overdiagnosis of PANDAS may have led to overuse of antibiotics to treat tics or OCD in the absence of active infection.

A single study of PANDAS patients showed efficacy of immunomodulatory therapy (intravenous immunoglobulin (IVIG) or plasma exchange) to symptoms, but these results are unreplicated by independent studies as of 2010. Kalra and Swedo wrote in 2009, "Because IVIG and plasma exchange both carry a substantial risk of adverse effects, use of these modalities should be reserved for children with particularly severe symptoms and a clear-cut PANDAS presentation. The US National Institutes of Health and American Academy of Neurology 2011 guidelines say there is "inadequate data to determine the efficacy of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS" and "insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS", adding that the investigators in the only study of plasmapherisis were not blind to the results. The Medical Advisory Board of the Tourette Syndrome Association said in 2006 that experimental treatments based on the autoimmune theory such as IVIG or plasma exchange should not be undertaken outside of formal clinical trials. The American Heart Association's 2009 guidelines state that, as PANDAS is an unproven hypothesis and well-controlled studies are not yet available, they do "not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (e.g., intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder".

Initial treatment is aimed at providing symptomatic relief. Benzodiazepines are the first line of treatment, and high doses are often required. A test dose of intramuscular lorazepam will often result in marked improvement within half an hour. In France, zolpidem has also been used in diagnosis, and response may occur within the same time period. Ultimately the underlying cause needs to be treated.

Electroconvulsive therapy (ECT) is an effective treatment for catatonia. Antipsychotics should be used with care as they can worsen catatonia and are the cause of neuroleptic malignant syndrome, a dangerous condition that can mimic catatonia and requires immediate discontinuation of the antipsychotic.

Excessive glutamate activity is believed to be involved in catatonia; when first-line treatment options fail, NMDA antagonists such as amantadine or memantine are used. Amantadine may have an increased incidence of tolerance with prolonged use and can cause psychosis, due to its additional effects on the dopamine system. Memantine has a more targeted pharmacological profile for the glutamate system, reduced incidence of psychosis and may therefore be preferred for individuals who cannot tolerate amantadine. Topiramate is another treatment option for resistant catatonia; it produces its therapeutic effects by producing glutamate antagonism via modulation of AMPA receptors.

There is limited evidence that caffeine, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.