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

Medications for schizophrenia are often used, especially when positive symptoms are present. Both first-generation antipsychotics and second-generation antipsychotics may be useful. Cognitive behavioral therapy has also been used.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

Individual therapy may be best suited to treat the individual's delusions. Persistence is needed in establishing a therapeutic empathy without validating the patient’s delusional system or overtly confronting the system. Cognitive techniques that include reality testing and reframing can be used. Antipsychotics and other therapeutic drugs have been used with relative success.

There are few treatments for many types of hallucinations. However, for those hallucinations caused by mental disease, a psychologist or psychiatrist should be alerted, and treatment will be based on the observations of those doctors. Antipsychotic and atypical antipsychotic medication may also be utilized to treat the illness if the symptoms are severe and cause significant distress. For other causes of hallucinations there is no factual evidence to support any one treatment is scientifically tested and proven. However, abstaining from hallucinogenic drugs, stimulant drugs, managing stress levels, living healthily, and getting plenty of sleep can help reduce the prevalence of hallucinations. In all cases of hallucinations, medical attention should be sought out and informed of one's specific symptoms.

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.

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.

Once it has been positively identified, pharmacotherapy follows. Antipsychotic drugs are the frontrunners in treatment for Fregoli and other DMSs. In addition to antipsychotics, anticonvulsants and antidepressants are also prescribed in some treatment courses. If a Fregoli patient has other psychological disorders, treatment often results in the use of trifluoperazine.

In patients suffering from schizophrenia, grandiose and religious delusions are found to be the least susceptible to cognitive behavioral interventions. Cognitive behavioral intervention is a form of psychological therapy, initially used for depression, but currently used for a variety of different mental disorders, in hope of providing relief from distress and disability. During therapy, grandiose delusions were linked to patients' underlying beliefs by using inference chaining. Some examples of interventions performed to improve the patient's state were focus on specific themes, clarification of neologisms, and thought linkage. During thought linkage, the patient is asked repeatedly by the therapist to explain his/her jumps in thought from one subject to a completely different one.

Patients suffering from mental disorders that experience grandiose delusions have been found to have a lower risk of having suicidal thoughts and attempts.

A widely accepted treatment for the syndrome of subjective doubles has not been developed. Treatment methods for this disease sometimes include the prescription of antipsychotic drugs, however, the type of drug prescribed depends on the presence of other mental disorders. Antipsychotic drugs (also known as neuroleptics) such as risperidone, pimozide, or haloperidol may be prescribed to treat the underlying psychiatric illness.

In addition to drug therapy, interpersonal counseling has also been suggested as a method to ease relations between the patient and his/her suspected doubles. However, the relationship between the patient and his/her double is not always negative.

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.

Some critical psychiatrists criticize the practice of defining one and the same belief as normal in one culture and pathological in another culture for cultural essentialism. They argue that since cultural influences are mixed, including not only parents and teachers but also peers, friends, books and the internet, and the same cultural influence can have different effects depending on earlier cultural influences, the assumption that culture can be boiled down to a few traceable, distinguishable and statistically quantifiable factors and that everything that does not fall in those factors must be biological, is not a justified assumption. Other critical psychiatrists argue that just because a person's belief is unshaken by one influence does not prove that it would remain unshaken by another. For example, a person whose beliefs are not changed by verbal correction from a psychiatrist, which is how delusion is usually diagnosed, may still change his or her mind when observing empirical evidence, only that psychiatry rarely if ever present patients with such situations.

Because of reduced levels of trust, there can be challenges in treating PPD. However, psychotherapy, antidepressants, antipsychotics and anti-anxiety medications can play a role when an individual is receptive to intervention.

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.