Abstract

Psychosis is a state of mind in which a person loses contact with reality in at least one important respect while not intoxicated with, or withdrawing from, alcohol or drugs, and while not affected by an acute physical illness that better accounts for the symptoms. Psychosis can be caused by a range of underlying conditions including schizophrenia, schizoaffective disorder, severe depression, severe mania (in bipolar disorder), delusional disorder and alcohol or substance misuse in the longer term. It can also be related to organic problems (e.g. brain tumours), trauma, stress or the side effects of medication (e.g. steroids) and may occur in patients with delirium and up to half of patients with dementia. Common positive symptoms of psychosis include delusions and hallucinations. These symptoms are strongly influenced by the underlying cause of the psychosis: delusions in schizophrenia tend to be bizarre; delusions in depression negative; delusions in mania expansive. Common negative symptoms include difficulties concentrating, anxiety, depressed mood, poor sleep, suspiciousness and social withdrawal. When a patient presents with psychotic symptoms, it is important to take a full psychiatric history, perform a mental state examination and complete relevant investigations, as indicated in each individual case. Following assessment, a vast majority, if not all, people with psychosis will be referred to specialist mental health services, often on an urgent basis, for further assessment, diagnosis and management. Generally, psychotic symptoms alone are sufficient reason for referral, but additional reasons include disturbed behaviour, suicidality, treatment resistance or failure of outpatient care.

Psychosis is a state of mind in which a person loses contact with  reality in at least one important respect while not intoxicated with, or withdrawing from, alcohol or drugs, and while not affected by an acute physical illness that better accounts for the symptoms. Approximately 3% of the population are affected by psychotic disorders.¹

Presentation

People with psychosis can present in primary care with both positive and negative symptoms.² Positive symptoms mean that the patient is having an additional experience that others do not share, while negative symptoms reflect a deficit.

Common positive symptoms of psychosis include delusions and hallucinations (see table 1). These symptoms are strongly influenced by the underlying cause of the psychosis: delusions in schizophrenia tend to be bizarre; delusions in depression negative; delusions in mania expansive.

Common negative symptoms of psychosis that GPs should look for include difficulties concentrating, anxiety, depressed mood, poor sleep, suspiciousness and social withdrawal. These symptoms can be very subtle and can overlap with depression.

In practice, presentations with psychosis vary greatly. One person might present with a long history of quiet, paranoid delusions possibly for many years. Another might present

with a sudden onset of dramatic hallucinations commanding them to do certain things or go to certain places; such commands might be resisted or ignored but are usually either distressing or perplexing. Others might present with very vague symptoms, chiefly related to social withdrawal and self-isolation, and it might not be clear if the person is mentally ill, misusing drugs or simply choosing to live differently.

Underlying causes and risk factors

Psychosis is a symptom rather than an illness. It is caused by a range of underlying conditions including schizophrenia, schizoaffective disorder, severe depression, severe mania (in bipolar disorder), delusional disorder and alcohol or substance misuse (in the longer term). It can also be related to organic problems (e.g. brain tumours), trauma, stress or the side effects of medication (e.g. steroids), and may occur in patients with delirium and up to half of patients with dementia (e.g. Alzheimer’s disease or Parkinson’s disease).

The causes of psychosis are not fully understood. However, psychosis is likely to be multifactorial in origin. Schizophrenia is a good example because it probably results from a complex interaction of inherited genes, disruptions to brain development in utero and further contributory factors acting in childhood, adolescence and early adulthood.³

There appear to be multiple genes involved, possibly leading to dysregulation of dopamine and other neurotransmitters. There are also links between schizophrenia and birth injuries, season of birth (winter and early spring), psychological trauma in childhood, cannabis use, head injury, migration, social adversity and living in cities.^4-6

Similar complex models of causation probably apply to other causes of psychosis, such as severe depression, mania in bipolar disorder and schizoaffective disorder (which includes both mood symptoms and features of schizophrenia).

Perhaps the clearest cause of psychosis identified to date is cannabis use. In 2017, the US National Academies of Sciences, Engineering and Medicine reviewed the evidence and concluded that the greater the use of cannabis, the greater the risk of psychosis.⁷ This confirms clinical experience and highlights the particular dangers of the high potency cannabis products currently available.^8,9 Daily cannabis use is associated with a three-fold increase in the odds of developing a psychotic disorder; daily use of high-potency cannabis is associated with a five-fold increase; and high-potency cannabis now accounts for at least 12% of cases of first-episode psychosis.¹⁰

Diagnosis

When someone presents with psychotic symptoms, it is important to take a full psychiatric history, perform a mental state examination and complete relevant investigations, as indicated in each individual case (see table 2).

In addition to the general history, useful questions include:

• Do you have any unusual experiences that other people possibly do not have?

• Do you hear voices talking to you when there is nobody there?

• Are people trying to hurt or harm you in any way?

Gaining the patient’s trust can be challenging, especially during a busy clinic. It is important to listen carefully and actively, maintain a calm approach (even if the patient is agitated) and remain unflustered by whatever the patient says (however unusual it may be). Building a good relationship with the patient is more important than eliciting all the information at one consultation.

Blood testing is appropriate in specific cases including suspected drug misuse (blood toxicology), suspected delirium (full blood count, kidney and liver function) or suspected endocrine disorder (thyroid disease).

Following assessment, a great majority, if not all, people with psychosis will be referred to specialist mental health services, often on an urgent basis, for further assessment, diagnosis and management.

Generally, psychotic symptoms alone are sufficient reason for referral, but additional reasons include disturbed behaviour, suicidality, treatment resistance or failure of outpatient care. Ongoing care will often involve both specialist mental health services and GPs.

Evidence-based management

Psychosis is a treatable condition. As with all mental disorders, treatment is based on a biopsychosocial approach: biological interventions include administration of medications, treatment of coexisting medical illness or substance misuse problems, and, in a small minority of cases, electroconvulsive therapy (ECT). Psychological and social interventions include specific psychotherapies for patients and families, as well as enhancing personal support and social participation.

Certain aspects of treatment will depend on the cause of the psychosis: depressive psychosis may require antipsychotic and/or antidepressant medication; severe mania in bipolar disorder may require antipsychotic and/or mood stabilising medication; schizophrenia will likely require antipsychotic medication and a range of other measures; and substance misuse may require antipsychotic medication in the short term and counselling or rehabilitation in the longer term.

Specialist care is usually required for specific groups such as children with psychosis, people with comorbid intellectual disability, patients with paraphrenia (organised delusional systems without deterioration of intellect or personality) and postpartum mental illness, which can involve psychosis.¹¹

NICE places especially strong emphasis on early intervention for first episode psychosis, for which it recommends medication in conjunction with psychological interventions such as family interventions and individual cognitive behaviour therapy (CBT).¹²

The choice of medication should be made jointly by the patient, healthcare professional and, if appropriate, carer, taking account of likely benefits and possible side effects such as weight gain, movement problems (e.g. restlessness), and potential metabolic, cardiac or hormonal effects (e.g. raised prolactin).

Older, first generation (typical) antipsychotic medications include fluphenazine, flupentixol, haloperidol, zuclopenthixol, sulpiride and pimozide. Newer, second generation (atypical) antipsychotics include risperidone, olanzapine, quetiapine, aripiprazole, amisulpride, ziprasidone and paliperidone. In practice, psychosis is now most often treated with a second generation antipsychotic medication, though first generation antipsychotics are still sometimes used. These newer second generation agents appear to be as effective as older agents in the management of delusions and hallucinations, with fewer adverse effects at recommended doses.

Side effects can include weight gain, impaired glucose tolerance and diabetes mellitus, as well as dry mouth, sedation, possible cardiac effects, dizziness and impotence. With all antipsychotics, neuroleptic malignant syndrome can occur; this is a rare adverse effect (very high temperature, confusion, muscle rigidity, perspiration, tachycardia) that needs to be managed in hospital and can be fatal if not treated.

It is recommended that, prior to commencing these medications, all patients should have: an ECG, weight and height checked, and a set of basic blood tests, including blood glucose. These should be monitored annually.

In first episode psychosis, the duration of trial of an antipsychotic will vary depending on the diagnosis; e.g. for schizophrenia, a six-week trial of an optimal dosage of a second generation medication should be combined with appropriate social and psychological treatment. If clinical results are not satisfactory after the trial period, therapeutic options should be reviewed and discussed with the patient and the family. Hallucinations (usually visual) are especially common in dementia and low-dose second generation antipsychotics can be used with caution and specialist advice.

It is important to establish if the patient is not taking the medication for any reason, and to address whatever concerns might be leading to this. Another antipsychotic medication (tablets or injections) can be tried for another trial period.

In the unlikely event that these steps do not produce sufficient clinical improvement, additional measures may be needed, depending on the cause of the psychosis. For example, clozapine is an antipsychotic medication that can greatly help people with difficult-to-treat schizophrenia, but it is reserved for treatment-resistant situations as it may cause agranulocytosis.

Both clozapine and ECT are prescribed by specialist mental health services and are limited to certain, well defined clinical circumstances.¹⁴

Ongoing treatment

Even if response to treatment is good following a first episode of psychosis in mental illness, there is a high risk of relapse if medication is stopped within one to two years.

Ongoing management of a long-term psychotic illness involves much more than medication, and requires a multidisciplinary team working together. Psychoeducation for the patient and family helps develop understanding of mental illness and its treatment, and enhances the therapeutic alliance between the patient, family and healthcare providers.

Other psychological approaches include CBT, family therapy, art therapy, social support, occupational therapy and self-help groups, such as the Hearing Voices Network, see Useful information, right.

Continued care for physical health is especially important. Men with schizophrenia die 15 years earlier, and women 12 years earlier, than the rest of the population.¹⁵ This excess is not accounted for by unnatural deaths; the leading causes are heart disease and cancer. As a result, there needs to be sustained focus on physical health, including support in stopping smoking, promotion of improved diet and lifestyle, and screening for cardiac risk factors (e.g. cholesterol, high blood pressure).