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.

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.

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 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.

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.

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.

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.

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.

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.

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.

In most cases hospital admission is necessary. Antipsychotic drugs and mood stabilizing drugs such as lithium are typically administered but is not clear if mood stabilizers can be titrated to a high enough level quickly enough to be effective. Electroconvulsive therapy may be considered, especially if there is a high risk of suicide.

Family support may be provided via a social worker.

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.

Treatment of secondary forms of delusional parasitosis are addressed by treating the primary associated psychological or physical condition. The primary form is treated much as other delusional disorders and schizophrenia. In the past, pimozide was the drug of choice when selecting from the typical antipsychotics. Currently, atypical antipsychotics such as olanzapine or risperidone are used as first line treatment.

However, it is also characteristic that sufferers will reject the diagnosis of delusional parasitosis by medical professionals, and very few are willing to be treated, despite demonstrable efficacy of treatment.

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.

For women taking psychiatric medication, the decision as to whether continue during pregnancy and whether to take them while breast feeding is difficult in any case; there is no data to guide this decision with respect to preventing postpartum psychosis. There is no data to guide a decision as to whether women at high risk for postpartum psychosis should take antipsychotic medicine to prevent it. For women at risk of postpartum psychosis, informing medical care-givers, and monitoring by a psychiatrist during pregnancy, in the perinatal period, and for a few weeks following delivery, is recommended.

For women with known bipolar disorder, taking medication during pregnancy roughly halves the risk of a severe postpartum episode, as does starting to take medication immediately after the birth.

Generally, a person experiencing a psychedelic crisis can be helped either to resolve the impasse, to bypass it, or, failing that, to terminate the experience. A person's thoughts before taking or while under the influence of the psychedelic, often greatly influence the trip.

Medical treatment consists of supportive therapy and minimization of external stimuli. In some cases, sedation is used when necessary to control self-destructive behavior, or when hyperthermia occurs. Diazepam is the most frequently used sedative for such treatment, but other benzodiazepines such as lorazepam are also effective. Such sedatives will only decrease fear and anxiety, but will not subdue hallucinations. In severe cases, antipsychotics such as haloperidol can reduce or stop hallucinations. Haloperidol is effective against drug-induced psychosis caused by LSD and other tryptamines, amphetamines, ketamine and phencyclidine.

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 are currently no antidepressants that are FDA approved for use during lactation. Most antidepressants are excreted in breast milk. However, there are limited studies showing the effects and safety of these antidepressants on breastfed babies.

There have been a few studies of medications for treating PPD, however, the sample sizes were small, thus evidence is generally weak. Some evidence suggests that mothers with PPD will respond similarly to people with major depressive disorder. There is evidence which suggests that selective serotonin reuptake inhibitors (SSRIs) are effective treatment for PPD. However, a recent study has found that adding sertraline, an SSRI, to psychotherapy does not appear to confer any additional benefit. Therefore, it is not completely clear which antidepressants, if any, are most effective for treatment of PPD, and for whom antidepressants would be a better option than non-pharmacotherapy.

Some studies show that hormone therapy may be effective in women with PPD, supported by the idea that the drop in estrogen and progesterone levels post-delivery contribute to depressive symptoms. However, there is some controversy with this form of treatment because estrogen should not be given to people who are at higher risk of blood clots, which include women up to 12 weeks after delivery. Additionally, none of the existing studies included women who were breastfeeding.

Aside from discontinuation of glucocorticoid medication, potential treatments discussed in the research literature include:

- anti-glucocorticoids

- psychoactive drugs that up-regulate the GRII glucocorticoid receptor:

- tricyclic antidepressants: Desipramine, Imipramine, and Amitriptyline (SSRIs do not )

- serotonin antagonists: Ketanserin

- mood stabilizers: Lithium

- corticotropin-releasing hormone (CRH) antagonists

- glutamate antagonists

- dehydroepiandrosterone (DHEA)

- small molecule brain-derived neurotrophic factor (BDNF) analogs

- stress reduction therapies and exercise.

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.

Only a small proportion of those with co-occurring disorders actually receive treatment for both disorders. Therefore, it was argued that a new approach is needed to enable clinicians, researchers and managers to offer adequate assessment and evidence-based treatments to patients with dual pathology, who cannot be adequately and efficiently managed by cross-referral between psychiatric and addiction services as currently configured and resourced. In 2011, it was estimated that only 12.4% of American adults with co-occurring disorders were receiving both mental health and addictions treatment. Clients with co-occurring disorders face challenges accessing treatment, as they may be excluded from mental health services if they admit to a substance abuse problem, and vice versa.

There are multiple approaches to treating concurrent disorders. Partial treatment involves treating only the disorder that is considered primary. Sequential treatment involves treating the primary disorder first, and then treating the secondary disorder after the primary disorder has been stabilized. Parallel treatment involves the client receiving mental health services from one provider, and addictions services from another.

Integrated treatment involves a seamless blending of interventions into a single coherent treatment package developed with a consistent philosophy and approach among care providers. With this approach, both disorders are considered primary. Integrated treatment can improve accessibility, service individualization, engagement in treatment, treatment compliance, mental health symptoms, and overall outcomes. The Substance Abuse and Mental Health Services Administration in the United States describes integrated treatment as being in the best interests or clients, programs, funders, and systems. Green suggested that treatment should be integrated, and a collaborative process between the treatment team and the patient. Furthermore, recovery should to be viewed as a marathon rather than a sprint, and methods and outcome goals should be explicit.

Although many patients may reject medications as antithetical to substance-abuse recovery and side effects, they can be useful to reduce paranoia, anxiety, and craving. Medications that have proven effective include opioid replacement therapies, such as lifelong maintenance on methadone or buprenorphine, to minimize risk of relapse, fatality, and legal trouble amongst opioid addicts, as well as helping with cravings, baclofen for alcoholics, opioid addicts, cocaine addicts, and amphetamine addicts, to help eliminate drug cravings, and clozapine, the first atypical antipsychotic, which appears to reduce illicit drug use amongst stimulant addicts. Clozapine can cause respiratory arrest when combined with alcohol, benzodiazepines, or opioids, so it is not recommended to use in these groups.

Intramuscular midazolam, lorazepam, or another benzodiazepine can be used to both sedate agitated patients, and control semi-involuntary muscle movements in cases of suspected akathisia.

Droperidol, haloperidol, or other typical antipsychotics can decrease the duration of agitation caused by acute psychosis, but should be avoided if the agitation is suspected to be akathisia, which can be potentially worsened. Also using promethazine may be useful.

In those with psychosis causing agitation there is a lack of support for the use of benzodiazepines, although they can prevent side effects associated with dopamine antagonists.

The condition usually resolves spontaneously within a timespan of weeks to months, with the severity of the symptoms reducing continuously over the period in question. A primary goal of treatment is to prevent patients from harming themselves or others during the episode.

Jungians emphasise the importance of recognising the patient's perspective throughout the episode, the danger being that

'if psychiatry itself considers the situation incomprehensible...many exclusion mechanisms will be set to work and [s]he will slide down the slope of a deeper and deeper regression'.

R. D. Laing pointed repeatedly to "the possibility that what we call psychosis may be sometimes a natural process of healing (a view for which I claim no priority)". Under the title "A Ten Day Voyage", he published an acquaintance's first-hand account of a reactive psychosis, triggered by a festering dog-bite. The protagonist reported

'"living in a - in another time dimension added to the time situation in which I am now...another sphere, another layer of existence lying above...the present"'.

At the close of the experience, the patient '"thought, well, somewhere or other I've got to sort of join up with my present - er - self, very strongly. So I...kept on saying my own name over and over again and all of a sudden, just like that - I suddenly realized that it was all over"'.

Psychologist Erik H. Erikson considered that whatever the causes, the psychotic break involved a primitive re-testing of the boundaries of self and other, words and meanings, in an effort to re-establish a new social mutuality.