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.

A number of psychosocial interventions may be useful in the treatment of schizophrenia including: family therapy, assertive community treatment, supported employment, cognitive remediation, skills training, token economic interventions, and psychosocial interventions for substance use and weight management. Family therapy or education, which addresses the whole family system of an individual, may reduce relapses and hospitalizations. Evidence for the effectiveness of cognitive-behavioral therapy (CBT) in either reducing symptoms or preventing relapse is minimal. Evidence for metacognitive training is mixed with one 2016 review finding benefit and another not. Art or drama therapy have not been well-researched.

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.

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.

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.

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.

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.

Research suggests that paraphrenics respond well to antipsychotic drug therapy if doctors can successfully achieve sufficient compliance. Herbert found that Stelazine combined with Disipal was an effective treatment. It promoted the discharging of patients and kept discharged patients from being readmitted later. While behavior therapy may help patients reduce their preoccupation with delusions, psychotherapy is not currently of primary value.

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.

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.

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.

STPD is rarely seen as the primary reason for treatment in a clinical setting, but it often occurs as a comorbid finding with other mental disorders. When patients with STPD are prescribed pharmaceuticals, they are most often prescribed the same drugs used to treat patients suffering from schizophrenia including traditional neuroleptics such as haloperidol and thiothixene. In order to decide which type of medication should be used, Paul Markovitz distinguishes two basic groups of schizotypal patients:

- Schizotypal patients who appear to be almost schizophrenic in their beliefs and behaviors (aberrant perceptions and cognitions) are usually treated with low doses of antipsychotic medications, e.g. thiothixene. However, it must be mentioned that long-term efficacy of neuroleptics is doubtful.

- For schizotypal patients who are more obsessive-compulsive in their beliefs and behaviors, SSRIs like Sertraline appear to be more effective.

Lamotrigine, an anti-convulsant, appears to be helpful in dealing with social isolation.

According to Theodore Millon, the schizotypal is one of the easiest personality disorders to identify but one of the most difficult to treat with psychotherapy. Persons with STPD usually consider themselves to be simply eccentric, productive, or nonconformist. As a rule, they underestimate maladaptiveness of their social isolation and perceptual distortions. It is not so easy to gain rapport with people who suffer from STPD due to the fact that increasing familiarity and intimacy usually increase their level of anxiety and discomfort. In most cases they do not respond to informality and humor.

Group therapy is recommended for persons with STPD only if the group is well structured and supportive. Otherwise, it could lead to loose and tangential ideation. Support is especially important for schizotypal patients with predominant paranoid symptoms, because they will have a lot of difficulties even in highly structured groups.

Research efforts are focusing on prevention in identifying early signs from relatives with associated disorders similar with schizophrenia and those with prenatal and birth complications. Prevention has been an ongoing challenge because early signs of the disorder are similar to those of other disorders. Also, some of the schizophrenic related symptoms are often found in children without schizophrenia or any other diagnosable disorder.

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.

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.

This form of schizophrenia is typically associated with early onset (often between the ages of 15 and 25 years) and is thought to have a poor prognosis because of the rapid development of negative symptoms and decline in social functioning.

Use of electroconvulsive therapy has been proposed; however, the effectiveness after treatment is in question.

Individuals who develop paraphrenia have a life expectancy similar to the normal population. Recovery from the psychotic symptoms seems to be rare, and in most cases paraphrenia results in in-patient status for the remainder of the life of the patient. Patients experience a slow deterioration of cognitive functions and the disorder can lead to dementia in some cases, but this development is no greater than the normal population.

Medical studies conclude that certain adjunctive drugs effectively palliate the negative symptoms of schizophrenia, mainly alogia. In one study, Maprotiline produced the greatest reduction in alogia symptoms with a 50% decrease in severity. Of the negative symptoms of schizophrenia, alogia had the second best responsiveness to the drugs, surpassed only by attention deficiency. D-amphetamine is another drug that has been tested on people with schizophrenia and found success in alleviating negative symptoms. This treatment, however, has not been developed greatly as it seems to have adverse effects on other aspects of schizophrenia such as increasing the severity of positive symptoms.

Although medication is the first-line treatment for most psychiatric disorders, it does not always improve every aspect of a patient's life, and for the negative symptoms in schizophrenia, the responses to anti-psychotics are less favourable than for positive symptoms. As a result, psychotherapy might be an alternative for the treatment of these symptoms, even if medication has a good effect on other manifestations of the disorder.

Cognitive behavioural therapy (CBT), is the kind of psychotherapy that shows most promise in treating avolition (and other negative symptoms of schizophrenia), but more research is needed in the area. CBT focuses on understanding how thoughts and feelings influence behaviour, in order to help individuals develop methods and strategies to better handle the implications of their disorder. Some research suggests that CBT focusing on social skills and practice of interpersonal situations, like job interviews, seeing a doctor (to discuss medication, for example), or interacting with friends and co-workers, as well as seemingly simple things like riding a bus, might reduce negative symptoms of schizophrenia and be beneficial to patients with avolition.

Other forms of psychotherapy might also complement the role of medication and help patients, their families, and friends to work through emotional and other challenges of living with a chronic psychological disorder, including avolition.

When pseudoneurotic schizophrenia was still being utilized as a diagnostic term, doctors were expected to be able to magically cure patients. Patients usually had very little understanding of themselves and the complexity of their illness. They were willing to employ any process in order to maintain mental stability. Their perception of mental stability, however, was also impaired, which made it much more difficult to make proper, helpful medication prescriptions.

Patients would often misuse medication in order to receive attention from their families. They would describe the dosage and effects of the medicine in some strange demeanor to demonstrate that their illness was physical rather than psychological. In like manner, taking medication also kept doctors concerned about the possibility of the patient developing substance dependence and/or drug addiction. Patients used this to get attention and sympathy from others.

There is no clear cause to how certain patients with schizophrenia develop post-schizophrenic depression while others may surpass this stage. However, there are a few theories as to possible causes. Those suffering from post-schizophrenic depression often suffer from social isolation due to their illness, which may increase depression levels. There is strong evidence of stigma-related isolation against those suffering from mental illnesses in a variety of societies, especially those with schizophrenia as they are often viewed as dangerous and unpredictable. Because of this isolation and studies linking social isolation and depression, it is possible that patients under these stigmas eventually develop post-schizophrenic depression. Depression in patients with schizophrenia may also be caused by substance abuse, which is fairly common among those suffering from schizophrenia, as depressants such as alcohol and cannabis can relax the patient. Furthermore, with what little information is currently known about post-schizophrenic depression, the onset may be caused by not giving patients with schizophrenia antipsychotic medications. After being taken off of antipsychotic medication, schizophrenic patients' antidepressant medication had to be increased, while those under antipsychotic medication reported suffering fewer depressive symptoms, further giving reason to believe that a lack of antipsychotic medication in earlier stages of schizophrenia may lead to post-schizophrenic depression. However, some psychology professionals still push for the reduction of neuroleptic drugs, as there is a popular belief that post-schizophrenic depression is caused by neuroleptic treatment. Therapists are also believed to engage the depression in people with schizophrenia, having given too much psychotherapy after the patient had overcome their schizophrenic symptoms. Schizophrenia itself should not be overlooked as a key player in causing post-schizophrenic depression, though. A study done over a two-year time period shadowing patients with schizophrenia and monitoring their depression was unable to locate possible triggers such as the ones previously listed, so it is possible the nature of schizophrenia itself is the primary cause of post-schizophrenic depression.

Oneirophrenic patients are resistant to insulin and when injected with glucose, these patients take 30 to 50% longer to return to normal glycemia. The meaning of this finding is not known, but it has been hypothesized that it may be due to an insulin antagonist present in the blood during psychosis. However, There is currently no known treatment for oneiophrenia.

Sluggish schizophrenia or slow progressive schizophrenia (, "vyalotekushchaya shizofreniya") was a diagnostic category used in Soviet Union to describe what they claimed was a form of schizophrenia characterized by a slowly progressive course; it was diagnosed even in a patient who showed no symptoms of schizophrenia or other psychotic disorders, on the assumption that these symptoms would appear later. It was developed in the 1960s by Soviet psychiatrist Andrei Snezhnevsky and his colleagues, and was used exclusively in the USSR and several Eastern Bloc countries, until the fall of Communism starting in 1989. The diagnosis has long been discredited because of its scientific inadequacy and its use as a means of confining dissenters. It has never been used or recognized outside of Soviet Union, or by international organizations such as the World Health Organization. It is considered a prime example of the political abuse of psychiatry in the Soviet Union.

Sluggish schizophrenia was the most infamous of diagnoses used by Soviet psychiatrists, due to its usage against political dissidents. After being discharged from a hospital, persons diagnosed with sluggish schizophrenia were deprived of their civic rights, credibility and employability. The usage of this diagnosis has been internationally condemned.

In the Russian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10), which has long been used throughout present-day Russia, sluggish schizophrenia is no longer listed as a form of schizophrenia, but it is still included as a schizotypal disorder in section F21 of chapter V.

According to Sergei Jargin, the same Russian term "vyalotekushchaya" for sluggish schizophrenia continues to be used and is now translated in English summaries of articles not as "sluggish" but as "slow progressive".