Psychosis is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis "cannot" be considered a symptom of a psychiatric disorder until other relevant and known causes of psychosis are properly excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.

An initial assessment includes a comprehensive history and physical examination by a physician, psychiatrist, psychiatric nurse practitioner or psychiatric physician assistant. Biological tests should be performed to exclude psychosis associated with or caused by substance use, medication, toxins, surgical complications, or other medical illnesses.

Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors, including medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:

- Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,

- Basic electrolytes and serum calcium to rule out a metabolic disturbance,

- Full blood count including ESR to rule out a systemic infection or chronic disease, and

- Serology to exclude syphilis or HIV infection.

Other investigations include:

- EEG to exclude epilepsy, and an

- MRI or CT scan of the head to exclude brain lesions.

Because psychosis may be precipitated or exacerbated by common classes of medications, medication-induced psychosis should be ruled out, particularly for first-episode psychosis. Both substance- and medication-induced psychosis can be excluded to a high level of certainty, using a

- Urinalysis and a

- Full serum toxicology screening.

Because some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests, a psychotic individual's family, partner, or friends should be asked whether the patient is currently taking any dietary supplements.

Common mistakes made when diagnosing people who are psychotic include:

- Not properly excluding delirium,

- Not appreciating medical abnormalities (e.g., vital signs),

- Not obtaining a medical history and family history,

- Indiscriminate screening without an organizing framework,

- Missing a toxic psychosis by not screening for substances "and" medications

- Not asking family or others about dietary supplements,

- Premature diagnostic closure, and

- Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.

Only after relevant and known causes of psychosis are excluded, a mental health clinician may make a psychiatric differential diagnosis using a person's family history, incorporating information from the person with psychosis, and information from family, friends, or significant others.

Types of psychosis in psychiatric disorders may be established by formal rating scales. The Brief Psychiatric Rating Scale (BPRS) assesses the level of 18 symptom constructs of psychosis such as hostility, suspicion, hallucination, and grandiosity. It is based on the clinician's interview with the patient and observations of the patient's behavior over the previous 2–3 days. The patient's family can also answer questions on the behavior report. During the initial assessment and the follow-up, both positive and negative symptoms of psychosis can be assessed using the 30 item Positive and Negative Symptom Scale (PANSS).

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

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.

Fink and Taylor developed a catatonia rating scale to identify the syndrome. A diagnosis is verified by a benzodiazepine or barbiturate test. The diagnosis is validated by the quick response to either benzodiazepines or electroconvulsive therapy (ECT). While proven useful in the past, barbiturates are no longer commonly used in psychiatry; thus the option of either benzodiazepines or ECT.

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.

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.

Schizophrenia is diagnosed based on criteria in either the American Psychiatric Association's (APA) fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM 5), or the World Health Organization's International Statistical Classification of Diseases and Related Health Problems (ICD-10). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a clinical assessment by a mental health professional. Symptoms associated with schizophrenia occur along a continuum in the population and must reach a certain severity and level of impairment, before a diagnosis is made. As of 2013 there is no objective test.

In the ICD-10 there are several disorders with the manic syndrome: organic manic disorder (), mania without psychotic symptoms (), mania with psychotic symptoms (), other manic episodes (), unspecified manic episode (), manic type of schizoaffective disorder (), bipolar affective disorder, current episode manic without psychotic symptoms (), bipolar affective disorder, current episode manic with psychotic symptoms ().

According to the DSM-5, "Catatonia Associated with Another Mental Disorder (Catatonia Specifier)" (code 293.89 [F06.1]) is diagnosed if the clinical picture is dominated by at least three of the following:

- stupor (i.e., no psychomotor activity; not actively relating to environment)

- catalepsy (i.e., passive induction of a posture held against gravity)

- waxy flexibility (i.e., allow positioning by examiner and maintain position)

- mutism (i.e., no, or very little, verbal response [exclude if known aphasia])

- negativism (i.e., opposition or no response to instructions or external stimuli)

- posturing (i.e., spontaneous and active maintenance of a posture against gravity)

- mannerisms (i.e., odd, circumstantial caricature of normal actions)

- stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements)

- agitation, not influenced by external stimuli

- grimacing (i.e. making a grimace like children)

- echolalia (i.e., mimicking another's speech)

- echopraxia (i.e., mimicking another's movements)

Other disorders (used additional code 293.89 [F06.1] to indicate the presence of the comorbid catatonia):

- Catatonia associated with autism spectrum disorder.

- Catatonia associated with schizophrenia spectrum and other psychotic disorders.

- Catatonia associated with brief psychotic disorder

- Catatonia associated with schizophreniform disorder

- Catatonia associated with schizoaffective disorder

- Catatonia associated with substance-induced psychotic disorder

- Catatonia associated with bipolar and related disorders.

- Catatonia associated with major depressive disorder

- Catatonic disorder due to another medical condition.

If catatonic symptoms are present but they are don't form the catatonic syndrome, a medication-induced or substance-induced aetiology should first be considered.

In 2013, the American Psychiatric Association released the fifth edition of the DSM (DSM-5). To be diagnosed with schizophrenia, two diagnostic criteria have to be met over much of the time of a period of at least one month, with a significant impact on social or occupational functioning for at least six months. The person had to be suffering from delusions, hallucinations, or disorganized speech. A second symptom could be negative symptoms, or severely disorganized or catatonic behaviour. The definition of schizophrenia remained essentially the same as that specified by the 2000 version of DSM (DSM-IV-TR), but DSM-5 makes a number of changes.

- Subtype classifications – such as catatonic and paranoid schizophrenia – are removed. These were retained in previous revisions largely for reasons of tradition, but had subsequently proved to be of little worth.

- Catatonia is no longer so strongly associated with schizophrenia.

- In describing a person's schizophrenia, it is recommended that a better distinction be made between the current state of the condition and its historical progress, to achieve a clearer overall characterization.

- Special treatment of Schneider's first-rank symptoms is no longer recommended.

- Schizoaffective disorder is better defined to demarcate it more cleanly from schizophrenia.

- An assessment covering eight domains of psychopathology – such as whether hallucination or mania is experienced – is recommended to help clinical decision-making.

The ICD-10 criteria are typically used in European countries, while the DSM criteria are used in the United States and to varying degrees around the world, and are prevailing in research studies. The ICD-10 criteria put more emphasis on Schneiderian first-rank symptoms. In practice, agreement between the two systems is high. The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom.

If signs of disturbance are present for more than a month but less than six months, the diagnosis of schizophreniform disorder is applied. Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, and various conditions may be classed as psychotic disorder not otherwise specified, while schizoaffective disorder is diagnosed if symptoms of mood disorder are substantially present alongside psychotic symptoms. If the psychotic symptoms are the direct physiological result of a general medical condition or a substance, then the diagnosis is one of a psychosis secondary to that condition. Schizophrenia is not diagnosed if symptoms of pervasive developmental disorder are present unless prominent delusions or hallucinations are also present.

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.

One study from as early as 1895 reported that approximately 10% of the population experiences hallucinations. A 1996-1999 survey of over 13,000 people reported a much higher figure, with almost 39% of people reporting hallucinatory experiences, 27% of which daytime hallucinations, mostly outside the context of illness or drug use. From this survey, olfactory (smell) and gustatory (taste) hallucinations seem the most common in the general population.

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.

Psychosis as a symptom of a psychiatric disorder is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis "cannot" be considered to be a symptom of a psychiatric disorder until other relevant and known medical causes of psychosis are excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.

An initial assessment includes a comprehensive history and physical examination. Although no biological laboratory tests exist which confirm schizoaffective disorder, biological tests should be performed to exclude psychosis associated with or caused by substance use, medications, toxins or poisons, surgical complications, or other medical illnesses. Since non-medical mental health practitioners are not trained to exclude medical causes of psychosis, people experiencing psychosis should be referred to an emergency department or hospital.

Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors which includes medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:

- Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,

- Basic electrolytes and serum calcium to rule out a metabolic disturbance,

- Full blood count including ESR to rule out a systemic infection or chronic disease, and

- Serology to exclude syphilis or HIV infection.

Other investigations which may be performed include:

- EEG to exclude epilepsy, and an

- MRI or CT scan of the head to exclude brain lesions.

Blood tests are not usually repeated for relapse in people with an established diagnosis of schizoaffective disorder, unless there is a specific "medical" indication. These may include serum BSL if olanzapine has previously been prescribed, thyroid function if lithium has previously been taken to rule out hypothyroidism, liver function tests if chlorpromazine has been prescribed, CPK levels to exclude neuroleptic malignant syndrome, and a urinalysis and serum toxicology screening if substance use is suspected. Assessment and treatment may be done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to self or others.

Because psychosis may be precipitated or exacerbated by common classes of psychiatric medications, such as antidepressants, ADHD stimulant medications, and sleep medications, prescribed medication-induced psychosis should be ruled out, particularly for first-episode psychosis. This is an essential step to reduce diagnostic error and to evaluate potential medication sources of further patient harm. Regarding prescribed medication sources of patient harm, Yale School of Medicine Professor of Psychiatry Malcolm B. Bowers, Jr, MD wrote:

Illicit drugs aren't the only ones that precipitate psychosis or mania—prescribed drugs can too, and in particular, some psychiatric drugs. We investigated this and found that about 1 in 12 psychotic or manic patients in an inpatient psychiatric facility are there due to antidepressant-induced psychosis or mania. That's unfortunate for the field [of psychiatry] and disastrous for some of our patients.

Substance-induced psychosis should also be ruled out. Both substance- and medication-induced psychosis can be excluded to a high level of certainty while the person is psychotic, typically in an emergency department, using both a

- Broad spectrum urine toxicology screening, and a

- Full serum toxicology screening (of the blood).

Some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests. So a psychotic person's family, partner, or friends should be asked whether he or she is currently taking any dietary supplements.

Common mistakes made when diagnosing psychotic patients include:

- Not properly excluding delirium,

- Missing a toxic psychosis by not screening for substances "and" medications,

- Not appreciating medical abnormalities (e.g., vital signs),

- Not obtaining a medical history and family history,

- Indiscriminate screening without an organizing framework,

- Not asking family or others about dietary supplements,

- Premature diagnostic closure, and

- Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.

Only after these relevant and known causes of psychosis have been ruled out can a psychiatric differential diagnosis be made. A mental health clinician will incorporate family history, observation of a psychotic person's behavior while the person is experiencing active symptoms, to begin a psychiatric differential diagnosis. Diagnosis also includes self-reported experiences, as well as behavioral abnormalities reported by family members, friends, or significant others. Mistakes in this stage include:

- Not screening for dissociative disorders. Dissociative identity disorder and psychotic symptoms in schizoaffective disorder have considerable overlap, yet a different overall treatment approach.

The same criteria are used to diagnose children and adults. Diagnosis is based on reports by parents or caretakers, teachers, school officials, and others close to the child.

A professional who believes a child has schizophrenia usually conducts a series of tests to rule out other causes of behavior, and pinpoint a diagnosis. Three different types of exams are performed: physical, laboratory, and psychological. Physical exams usually cover the basic assessments, including but not limited to; height, weight, blood pressure, and checking all vital signs to make sure the child is healthy. Laboratory tests include electroencephalogram EEG screening and brain imaging scans. Blood tests are used to rule out alcohol or drug effects, and thyroid hormone levels are tested to rule out hyper- or hypothyroidism. A psychologist or psychiatrist talks to a child about their thoughts, feelings, and behavior patterns. They also inquire about the severity of the symptoms, and the effects they have on the child's daily life. They may also discuss thoughts of suicide or self-harm in these one-on-one sessions. Some symptoms that may be looked at are early language delays, early motor development delays and school problems.

Many of persons with childhood schizophrenia are initially misdiagnosed as having pervasive developmental disorders (autism spectrum disorder, for example).

In the DSM-IV-TR, paranoia is diagnosed in the form of:

- paranoid personality disorder ()

- paranoid schizophrenia (a subtype of schizophrenia) ()

- the persecutory type of delusional disorder, which is also called "querulous paranoia" when the focus is to remedy some injustice by legal action. ()

According to clinical psychologist P. J. McKenna, "As a noun, paranoia denotes a disorder which has been argued in and out of existence, and whose clinical features, course, boundaries, and virtually every other aspect of which is controversial. Employed as an adjective, paranoid has become attached to a diverse set of presentations, from paranoid schizophrenia, through paranoid depression, to paranoid personality—not to mention a motley collection of paranoid 'psychoses', 'reactions', and 'states'—and this is to restrict discussion to functional disorders. Even when abbreviated down to the prefix para-, the term crops up causing trouble as the contentious but stubbornly persistent concept of paraphrenia".

At least 50% of the diagnosed cases of schizophrenia experience delusions of reference and delusions of persecution. Paranoia perceptions and behavior may be part of many mental illnesses, such as depression and dementia, but they are more prevalent in three mental disorders: paranoid schizophrenia, delusional disorder (persecutory type), and paranoid personality disorder.

A 2012 paper suggested that, when compared with experiences today, psychiatric conditions associated with psychotic spectrum symptoms may be possible explanations for some revelatory driven experiences and activities such as those of Abraham, Moses, Jesus, and Saint Paul. However, the paper admits that the study was not aimed to deny supernatural elements, nor was it conclusive on whether their experiences were delusional in part or not at all.

Examples from a 295-subject study in Lithuania showed that the most common religious delusions were being a saint (in women) and being God (in men).

In one study of 193 people who had previously been admitted to hospital and subsequently diagnosed with schizophrenia, 24% were found to have religious delusions.

A 1999 study identified that religious delusions were often present or expressed in persons with forensic committal to a psychiatric unit.

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.

In the ICD-10, Bouffée délirante is classified as a subtype of either Acute polymorphic psychotic disorder without symptoms of schizophrenia (F23.0) or Acute polymorphic psychotic disorder with symptoms of schizophrenia (F23.1).

"Bouffée délirante" literally means a "delirious flash".

In ICD-10, this disorder is called depersonalization-derealization syndrome F48.1. The diagnostic criteria are as follows:

The diagnosis should not be given in certain specified conditions, for instance when intoxicated by alcohol or drugs, or together with schizophrenia, mood disorders and anxiety disorders.

Bouffée délirante is a culture-bound syndrome in West Africa and Haiti of a sudden outburst of aggression, confusion and psychomotor excitement, possibly including visual or auditory hallucinations and paranoia.

The attribution model has been well talked about regarding paranoid or delusional individuals. The idea is that they like to assign issues to external events. A motivation behind this characteristic may involve the need for that person to develop a better self-image and maintain self-confidence. There have been debates about whether or not paranoid individuals are more likely to have a low or high self-perception, and results have been generated for both of these hypotheses. Researchers have made a distinction between positive self-esteem and negative self-esteem revealing that paranoid delusional individuals have more of a negative self-evaluation.

Diagnosis is based on the self-reported experiences of the person followed by a clinical assessment. Psychiatric assessment includes a psychiatric history and some form of mental status examination. Since some medical and psychiatric conditions mimic the symptoms of DPD, clinicians must differentiate between and rule out the following to establish a precise diagnosis: temporal lobe epilepsy, panic disorder, acute stress disorder, schizophrenia, migraine, drug use, brain tumour or lesion. No laboratory test for depersonalization-derealization disorder currently exists.

The diagnosis of depersonalization disorder can be made with the use of the following interviews and scales:

The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) is widely used, especially in research settings. This interview takes about 30 minutes to 1.5 hours, depending on individual's experiences.

The Dissociative Experiences Scale (DES) is a simple, quick, self-administered questionnaire that has been widely used to measure dissociative symptoms. It has been used in hundreds of dissociative studies, and can detect depersonalization and derealization experiences.

The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview which makes DSM-IV diagnoses of somatization disorder, borderline personality disorder and major depressive disorder, as well as all the dissociative disorders. It inquires about positive symptoms of schizophrenia, secondary features of dissociative identity disorder, extrasensory experiences, substance abuse and other items relevant to the dissociative disorders. The DDIS can usually be administered in 30–45 minutes.

The Cambridge Depersonalization Scale (CDS) is a method for determining the severity of depersonalization disorder. It has been proven and accepted as a valid tool for the diagnosis of depersonalization disorder in a clinical setting. It is also used in a clinical setting to differentiate minor episodes of depersonalization from actual symptoms of the disorder. Due to the success of the CDS, a group of Japanese researchers underwent the effort to translate the CDS into the J-CDS or the Japanese Cambridge Depersonalization Scale. Through clinical trials the Japanese research team successfully tested their scale and determined its accuracy. One limitation is that the scale does not allow for the differentiation between past and present episodes of depersonalization. It should also be noted that it may be difficult for the individual to describe the duration of a depersonalization episode, and thus the scale may lack accuracy. The project was conducted in the hope that it would stimulate further scientific investigations into depersonalization disorder.

Delusional parasitosis is divided into primary, secondary functional, and secondary organic groups.