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Editors

LauriTuominen
RaimoK.R.Salokangas

Schizophrenia

Essentials

  • When schizophrenia is suspected, specialized psychiatric care should be provided as early as possible, preferably before the first episode of psychosis.
  • Treatment aims to eliminate or alleviate symptoms, prevent new episodes of psychosis and improve psychosocial performance and quality of life.
  • Treatment consists of pharmacotherapy combined with psychosocial therapies. After the initial phase, the treatment is primarily delivered in outpatient care. In long-term treatment, active commitment of the patient, somatic health care and flexible services in case of crisis are important.
  • Patients with schizophrenia have a higher mortality rate than the normal population. Excess mortality is mainly due to suicide in young patients and cardiovascular, metabolic and respiratory diseases in older patients.

Aetiology

  • The stress-diathesis model may be used to explain the development of schizophrenia. According to this model, genetics and/or early development contribute to a predisposition towards the disease, and psychosocial and/or toxic (e.g. cannabis) stress factors trigger the disease.
  • The most important predisposing factor is genetic but only a small proportion of schizophrenic patients have a close relative with the same condition. Disturbed foetal development, complications of labour, childhood traumas and immigrant background may also increase the risk of schizophrenia.

Epidemiology

  • Schizophrenia usually starts in early adulthood, in men earlier than in women. It is also more common in men than in women (1.4:1).
  • The annual incidence of schizophrenia is approximately 2 cases per 1 000 inhabitants and its prevalence within the population is approximately 0.5-1.5%.

Diagnosis

  • Diagnosis is made by a psychiatrist with the assistance of a multidisciplinary team. The diagnostic workup consists of a clinical interview, family interview, physical and psychological, preferably neuropsychological, examinations.
  • In addition, the initial assessment includes assessment of social and occupational functioning and of the situation of the patient's children.
  • Diagnosis is based on the presence of symptoms typical for schizophrenia of at least one month's duration and reduced functional capacity.
  • Physical and laboratory investigations are used to rule out somatic diseases that may present with psychotic symptoms (for example, neurological and endocrinological diseases, see Mental Disorders Due to Somatic Disease) and psychosis induced by intoxicant abuse.

Symptoms

  • Patients with schizophrenia have positive and negative symptoms, as well as cognitive deficits.
  • Depression and anxiety often also occur in connection with schizophrenia.
  • In the acute phase, the patient almost always has hallucinations, delusions and incoherence.
  • A schizophrenic patient may be suicidal both during the acute phase and during the immediate postpsychotic recovery phase.
  • Schizophrenia is almost invariably associated with withdrawal from social contact and a diminished ability to study or work as well as reduced functional capacity.

Positive symptoms (hallucinations, delusions and incoherence)

  • Auditory hallucinations, particularly voices commenting on the patient's behaviour and discussing with each other, are typical. Somatic hallucinations are also possible; the patient may, for example, feel the presence of a device of some sort within the brain. Olfactory, gustatory and tactile hallucinations are also possible.
  • Visual hallucinations may also occur, especially in the early stage of the disease.
  • The most common delusions are delusions of persecution, delusions of reference and delusions of control. Patients may feel that they are being followed or persecuted, or that references or messages to them appear in newspapers or on the radio, or that they are being influenced by, for example, telepathic means. A severely paranoid patient may be dangerous.
  • Incoherence presents as inconsistency of thought, cessation in the flow of thought, abnormal associations and concretization of thought.

Negative symptoms

  • The negative symptoms of schizophrenia describe the lack of motivation and interest associated with the disorder, as well as flattening of expression.
    • Lack of motivation and interest manifest as inability to feel pleasure, lack of will, apathy and social withdrawal.
    • Flattening of expression appears as poverty of speech and reduced emotional expression.

Cognitive symptoms

  • Cognitive deficiencies occur with regard to e.g. attentiveness, executive function, memory, information processing and perception, as well as in general cognitive capacity.

Somatic comorbidities

  • Somatic diseases are common in patients with schizophrenia, such as cardiovascular or metabolic diseases (e.g. type 2 diabetes and MBO), low vitamin D concentration, impaired bone health, pulmonary or oral diseases.

Prodromal symptoms

  • Psychosis may be preceded by a phase during which anxiety and depression occur, as well as mild psychotic symptoms, such as feelings of change in one's environment or in oneself, or of being followed or observed, or short-lasting illusions or hallucinations. When suspecting prodromal symptoms, the patient should be referred for an evaluation within specialized care.
  • The recommended primary therapy for prodromal symptoms is cognitive-behavioural psychotherapy. If the symptoms are severe or progressive, it is worthwhile to start a second-generation antipsychotic drug, combined with the psychotherapy.
  • Anxiety and depression in a patient with prodromal symptoms should also be treated.

Basics of treatment Music Therapy for Schizophrenia or Schizophrenia-Like Illnesses, Social Skills Programmes for Schizophrenia, Electroconvulsive Therapy for Treatment-Resistant Schizophrenia

  • The cornerstone of treatment and rehabilitation is a long-term, understanding and trusting therapeutic relationship.
  • The treatment of schizophrenia should be patient-oriented and take into account the patient's individual needs. The treatment should be discussed with the patient unless the disease renders discussion impossible.
  • The treatment should be based on a written care plan reviewed at fixed intervals.
  • The aim of treatment and rehabilitation is to remove or alleviate symptoms, prevent the recurrence of episodes of psychosis or reduce their frequency and severity, as well as to improve psychosocial functioning, work ability and quality of life.
  • The treatment is primarily delivered in outpatient care Day Hospital Versus Admission for Acute Psychiatric Disorders, and the patient's family and close social network should be involved as far as possible.
  • In the treatment of schizophrenia one should be prepared for crisis situations, where the patient, for example, becomes ill with a somatic disease or in an unplanned manner drops out from care. Active approach and intensive support for the patient are required in such situations.
  • Antipsychotic drug treatment markedly decreases the symptoms of acute psychosis, new episodes of psychosis and mortality.
  • Combining psychosocial therapies with the drug treatment will alleviate symptoms, improve the patient's psychosocial functioning and prevent new episodes of psychosis and hospitalization Intensive Case Management for Severe Mental Illness Music Therapy for Schizophrenia or Schizophrenia-Like Illnesses.
  • Paying attention to the somatic health in examinations, treatment and follow-up is an essential part of good treatment of a patient with schizophrenia.

Acute care

Drug treatment Chlorpromazine Versus Placebo for Schizophrenia, Haloperidol Versus Placebo for Schizophrenia, Perazine for Schizophrenia, Aripiprazole for Schizophrenia, Risperidone Vs. other Atypical Antipsychotic Medication for Schizophrenia, Risperidone Versus Placebo for Schizophrenia, Trifluoperazine for Schizophrenia, Perphenazine for Schizophrenia, Zuclopenthixol Dihydrochloride for Schizophrenia, Depot Risperidone for Schizophrenia, Quetiapine for Schizophrenia, Pimozide for Schizophrenia or Related Psychoses, Atypical Antipsychotics for People with Both Schizophrenia and Depression, Haloperidol Versus First-Generation Antipsychotic Drugs for Schizophrenia, Antipsychotic Switching for People with Schizophrenia Who have Neuroleptic-Induced Weight or Metabolic Problems, Antipsychotic Switching for People with Schizophrenia Who have Neuroleptic-Induced Weight or Metabolic Problems, Asenapine Versus Placebo for Schizophrenia, Chlorpromazine Versus Atypical Antipsychotic Drugs for Schizophrenia, Clozapine Combined with Different Antipsychotic Drugs for Treatment-Resistant Schizophrenia

Psychotic stage

  • Antipsychotic drugs are effective in reducing the positive effects of schizophrenia. They act less effectively on the negative and cognitive symptoms.
  • The recommended daily dose for the treatment of the first episode of psychosis is, for example, 2-4 mg risperidone or 7.5-15 mg aripiprazole.
  • The recommended daily dose for the treatment of a recurrent episode of psychosis is, for example, 4-6 mg risperidone, 10-30 mg aripiprazole or 16-24 mg perphenazine.
  • When planning medication, it is important to bear in mind the patient's previous experience with drug treatment since the susceptibility to different types of adverse effects varies from patient to patient.
  • The lowest effective daily dose should be sought by gradually adjusting the dose. This will avoid the emergence of drug-induced adverse effects and improve compliance.

Maintenance treatment

  • The goal of maintenance therapy is the prevention of psychosis relapses Maintenance Treatment with Antipsychotic Drugs for Schizophrenia.
  • After the period of psychosis, the dosage should be gradually lowered under close monitoring of the patient's condition. When the maintenance dose has been achieved, the treatment may be continued either as tablets or as depot injections.
  • Doses used in long-term therapy are usually markedly lower than those used in acute situations. In long-term treatment of schizophrenia, the daily dose may be, for example, 2-5 mg risperidone or 10-20 mg olanzapine.
  • Depot antipsychotic drug injection is effective in reducing new hospitalizations and mortality. In depot injection treatment, the recommended doses are e.g. 25-50 mg risperidone every 2 weeks or 50-100 mg paliperidone or 300-400 mg aripiprazole at 1-month intervals.
  • Clozapine Clozapine Therapy is more effective than other antipsychotics. Its use is associated with lower mortality than that associated with other antipsychotics. Clozapine is the drug of choice in the treatment of schizophrenia refractory to other medication.
  • Usually patients with schizophrenia require long-term drug therapy. Prophylactic antipsychotic treatment against relapses should continue for at least 2-5 years even after treatment response has been achieved Maintenance Treatment with Antipsychotic Drugs for Schizophrenia.
  • Withdrawal of the medication must be gradual and the patient should be closely monitored for the emergence of symptoms predictive of psychosis. Should any such symptoms emerge, the medication should be increased to its earlier effective level.

Adjuvant drugs Valproate for Schizophrenia, Carbamazepine for Schizophrenia, Acetylcholinesterase Inhibitors for Schizophrenia, Electroconvulsive Therapy for Treatment-Resistant Schizophrenia

Adverse effects of the medication

  • Adverse effects of antipsychotics warrant specialist consultation.
  • The use of antipsychotics may be associated with parkinsonism and extrapyramidal symptoms, such as stiffness, dystonia or akathisia. Particular attention should be paid to involuntary muscular movements of the mouth, tongue, eyes and neck.
  • Acute neurological adverse effects of antipsychotic drugs should be treated with transient anticholinergic medication (e.g. 2-6 mg biperiden) and the antipsychotic medication or its dosage subsequently changed so that the adverse effects disappear.
  • Long-term anticholinergic medication should be avoided.
  • The use of all antipsychotics is associated with the risk of neuroleptic malignant syndrome Neuroleptic Malignant Syndrome (Nms).
  • Many antipsychotic drugs are associated with weight gain Antipsychotic Switching for People with Schizophrenia Who have Neuroleptic-Induced Weight or Metabolic Problems, elevated blood glucose values, insulin resistance and elevated blood lipid values.
  • All antipsychotics, particularly sertindole and ziprasidone, may increase cardiac QT interval Long QT Syndrome (LQTS).
  • In order to prevent metabolic adverse effects, to diagnose them and start their treatment early, the patient's physical health should be regularly monitored: the patient's body mass index, waist measurement, blood pressure, as well as glucose and lipid values must be measured/determined.
  • The use of antipsychotics is also associated with sexual adverse effects.

Other treatment

Psychotherapy Crisis Intervention for People with Severe Mental Illnesses, Social Skills Programmes for Schizophrenia

Family

  • The family and close social network of a patient with schizophrenia should be included in the care. Inclusion of the family will improve the patient's commitment to treatment, promote rehabilitation and help close relatives to overcome the crisis Family Interventions in Schizophrenia.
  • Inclusion of the family in a psychoeducational approach will reduce the recurrence of psychoses and the number of periods of hospital treatment and improve compliance with pharmacotherapy.
  • The situation of children in the family should also be investigated and measures appropriate in each situation taken in cooperation with experts in child psychiatry and with welfare authorities.

Rehabilitation Music Therapy for Schizophrenia or Schizophrenia-Like Illnesses

  • The possibilities of every patient with schizophrenia for vocational rehabilitation must be investigated and supported.
  • Supported employment ("place and rehabilitate") will improve the patient's chances for employment and coping in the open job market Supported Employment for Adults with Severe Mental Illness.
  • Training of social skills improves social functioning in a patient with schizophrenia.
  • Most patients with schizophrenia need residential rehabilitation.
  • Rehabilitation of cognitive functions, if the patient is in need of that, should be included and combined with the rest of the rehabilitation.

Health behaviour

Organization of care

  • The task allocation between primary and specialized health care depends on local circumstances and resources.
  • A schizophrenic patient seen for the first time must be referred to specialized care.
  • Patients with poorly controlled schizophrenia need specialized care. The treatment of patients whose disease is well controlled can be managed in primary care and a psychiatrist consulted as necessary.
  • Clozapine therapy Clozapine Therapy is started in specialized care. Follow-up treatment including monitoring of blood neutrophil counts can take place in primary care.

Prognosis

  • Schizophrenia is a serious and chronic disease.
  • More than half of schizophrenic patients will make a reasonable recovery, but about one in ten patients need help with daily activities.
  • The course of the disease is often variable: the patient may have repeated episodes of psychosis but may be almost free of symptoms in between times.
  • The age-adjusted mortality of schizophrenic patients is 2-3 times as high as in the general population. The excess mortality of patients with schizophrenia is mainly due to general diseases, such as cardiovascular, metabolic or respiratory diseases.
  • In younger age groups, the excess mortality compared to the general population is mainly due to suicides; 5% of patients with schizophrenia commit suicide.
  • Mortality is highest among patients not taking antipsychotic medication. Also long-term use of benzodiazepines increases mortality.

Monitoring the effectiveness of treatment

  • Following up the realization of treatments defined in the patient's treatment plan and monitoring the changes in his/her clinical and functional condition belong to the good treatment of a patient with schizophrenia.

    References

    • Aymerich C, Salazar de Pablo G, Pacho M, et al. All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis. Mol Psychiatry 2024;(): [PubMed]
    • McCutcheon RA, Keefe RSE, McGuire PK. Correction: Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol Psychiatry 2023;28(5):1919 [PubMed]
    • Correll CU, Solmi M, Croatto G, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry 2022;21(2):248-271 [PubMed]
    • D'Souza DC, DiForti M, Ganesh S, et al. Consensus paper of the WFSBP task force on cannabis, cannabinoids and psychosis. World J Biol Psychiatry 2022;23(10):719-742 [PubMed]
    • Vita A, Gaebel W, Mucci A, et al. European Psychiatric Association guidance on assessment of cognitive impairment in schizophrenia. Eur Psychiatry 2022;65(1):e58 [PubMed]
    • McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia-An Overview. JAMA Psychiatry 2020;77(2):201-210 [PubMed]
    • Fusar-Poli P, McGorry PD, Kane JM. Improving outcomes of first-episode psychosis: an overview. World Psychiatry 2017;16(3):251-265 [PubMed]
    • Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29823 Patients With Schizophrenia. JAMA Psychiatry 2017;74(7):686-693 [PubMed]
    • Schmidt SJ, Schultze-Lutter F, Schimmelmann BG, et al. EPA guidance on the early intervention in clinical high risk states of psychoses. Eur Psychiatry 2015;30(3):388-404. [PubMed]
    • Perälä J, Suvisaari J, Saarni SI, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007 Jan;64(1):19-28.

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