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.

Lithium and the anticonvulsants carbamazepine, lamotrigine, and valproic acid are used as mood stabilizers to treat bipolar disorder. These mood stabilizers are used for long-term mood stabilization but have not demonstrated the ability to quickly treat acute bipolar depression. Lithium is preferred for long-term mood stabilization. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or a more schizoaffective clinical picture. It is less effective in preventing relapse than lithium or valproate. Since then, valproate has become a commonly prescribed treatment, and is effective in treating manic episodes. Lamotrigine has some efficacy in treating bipolar depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. The effectiveness of topiramate is unknown.

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.

Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers. Olanzapine is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium.

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.

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.

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.

Several treatment guidelines recommend either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.

Pharmaceutical treatments can include tricyclic antidepressants, atypical antipsychotics, or a combination of an antidepressant from the newer, more well tolerated SSRI or SNRI categories and an atypical antipsychotic. Olanzapine may be an effective monotherapy in psychotic depression, although there is evidence that it is ineffective for depressive symptoms as a monotherapy; and olanzapine/fluoxetine is more effective. Quetiapine monotherapy may be particularly helpful in psychotic depression since it has both antidepressant and antipsychotic effects and a reasonable tolerability profile compared to other atypical antipsychotics. The current drug-based treatments of psychotic depression are reasonably effective but can cause side effects, such as nausea, headaches, dizziness, and weight gain. Tricyclic antidepressants are particularly dangerous in overdose due to their potential to cause potentially-fatal cardiac arrhythmias.

In the context of psychotic depression, the following are the most well-studied antidepressant/antipsychotic combinations

"First-generation"

- Amitriptyline/perphenazine

- Amitriptyline/haloperidol

"Second-generation"

- Venlafaxine/quetiapine?

- Olanzapine/fluoxetine

- Olanzapine/sertraline

In modern practice of ECT a therapeutic clonic seizure is induced by electric current via electrodes placed on an anaesthetised, unconscious patient. Despite much research the exact mechanism of action of ECT is still not known. ECT carries the risk of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.

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.

Psychological treatments such as acceptance and commitment therapy (ACT) are possibly useful in the treatment of psychosis, helping people to focus more on what they can do in terms of valued life directions despite challenging symptomology.

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.

A challenge in the treatment of delusional disorders is that most patients have limited insight, and do not acknowledge that there is a problem. Most patients are treated as out-patients, although hospitalization may be required in some cases if there is a risk of harm to self or others. Individual psychotherapy is recommended rather than group psychotherapy, as patients are often quite suspicious and sensitive. Antipsychotics are not well tested in delusional disorder, but they do not seem to work very well, and often have no effect on the core delusional belief. Antipsychotics may be more useful in managing agitation that can accompany delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders.

Psychotherapy for patients with delusional disorder can include cognitive therapy which is conducted with the use of empathy. During the process, the therapist can ask hypothetical questions in a form of therapeutic Socratic questioning. This therapy has been mostly studied in patients with the persecutory type. The combination of pharmacotherapy with cognitive therapy integrates treating the possible underlying biological problems and decreasing the symptoms with psychotherapy as well. Psychotherapy has been said to be the most useful form of treatment because of the trust formed in a patient and therapist relationship.

Supportive therapy has also been shown to be helpful. Its goal is to facilitate treatment adherence and provide education about the illness and its treatment.

Furthermore, providing social skills training has helped many persons. It can promote interpersonal competence as well as confidence and comfort when interacting with those individuals perceived as a threat.

Insight-oriented therapy is rarely indicated or contraindicated; yet there are reports of successful treatment. Its goals are to develop therapeutic alliance, containment of projected feelings of hatred, impotence, and badness; measured interpretation as well as the development of a sense of creative doubt in the internal perception of the world. The latter requires empathy with the patient's defensive position.

Efforts are made to find a treatment which targets the proposed specific underlying pathophysiology of psychotic depression. A promising candidate was mifepristone, which by competitively blocking certain neuro-receptors, renders cortisol less able to directly act on the brain and was thought to therefore correct an overactive HPA axis. However, a Phase III clinical trial, which investigated the use of mifepristone in PMD, was terminated early due to lack of efficacy.

Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways.

Research has shown that psychotic depression differs from non-psychotic depression in a number of ways: potential precipitating factors, underlying biology, symptomatology beyond psychotic symptoms, long-term prognosis, and responsiveness to psychopharmacological treatment and ECT.

The use of lithium and quetiapine (Seroquel) have both shown to be particularly valuable, though several other medications of the anticonvulsants and atypical antipsychotics classes may also be helpful.

- Lithium – Lithium has been shown to help stabilize the mood of patients suffering from cyclothymia and as well as bipolar disorders. It also aids in the prevention of acute suicidal and manic episodes. Dosage must be carefully monitored as lithium has a plethora of side effects.

- Atypical antipsychotics – (e.g., quetiapine (Seroquel), also olanzapine (Zyprexa), and risperidone (Risperdal).

- Anticonvulsants – (e.g., valproic acid, lamotrigine (Lamictal), and valproate semisodium (Depakote)).

- Electroconvulsive therapy – Through a systematic review done by Versiani, Cheriaux, and Landeira-Fernandez, it was determined that the efficacy and safety of ECT in patients with bipolar disorder had been poorly investigated and the evidence had methodological limitations.

There are few studies specifically testing psychotherapy for cyclothymia. The following is a list of some common types of therapy. They have different amounts of support for use with bipolar disorder and other mood disorders. If a treatment helps with bipolar disorder, it is a reasonable choice for use with cyclothymia until better evidence becomes available.

- Cognitive behavioural therapy (CBT) – Has been found to reduce depression.

- Dialectical behavioral therapy (DBT)

- Interpersonal psychotherapy (IT)

- Interpersonal and social rhythm therapy (IPSRT)

- Group therapy

- Integrative therapy

- Person-centered therapy (PCT)

- Psychodynamic therapy

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.

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 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.

It is possible for this disorder to progress over time. A patient suffering from the disorder can improve the condition with treatments. There are several types of therapies that may improve the condition, but depending on a patient’s experience of the disorder or the cause of the disorder, treatments will vary.

- Psychotherapy including behaviour therapy, Gestalt therapy, Adlerian therapy, psychoanalytic therapy and existential therapy.

- Pharmacotherapy through medications including antidepressants.

The article "Cotard's syndrome: A Review" (2010) reports successful pharmacological treatments (mono-therapeutic and multi-therapeutic) using antidepressant, antipsychotic, and mood stabilizing drugs; likewise, with the depressed patient, electroconvulsive therapy (ECT) is more effective than pharmacotherapy. Cotard syndrome resulting from an adverse drug reaction to valacyclovir is attributed to elevated serum concentration of one of valacyclovir's metabolites, 9-carboxymethoxymethylguanine (CMMG). Successful treatment warrants cessation of the drug, valacyclovir. Hemodialysis was associated with timely clearance of CMMG and resolution of symptoms.

Both psychotherapy as well as different drugs (e.g. serotonin reuptake inhibitors - SSRIs or mood stabilizers, e.g. lithium, antiepileptics) have been suggested as treatments. However, no randomized controlled treatment trial of RBD has been conducted.

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.