Apply Shared Decision Making: discuss benefits and risks and obtain patient preference.

Choose based on safety (mainly) and efficacy.

Consider prior response and avoid previous side-effects.

Select an antipsychotic that does not worsen comorbidities (e.g. obesity, hyperlipidemia, diabetes, renal/liver failure, cardiovascular issues).

Consider drug-drug interactions, click for websites

Some antipsychotics require food intake (lurasidone ≥350 kcal, ziprasidone ≥500 kcal), other antipsychotics should be taken at least one hour before eating (quetiapine extended-release).

Liquids, rapidly dissolving tablets, long-half life facilitate adherence

Sedative effects can be useful in agitated or insomniac patients

Think ahead: E.g. if long-acting injectable (LAI) is planned for relapse prevention, choose oral antipsychotic which is also available as LAI

Consider drug availability in your country

Consider recommendations for patient subgroups in Section "Special Situations"

Apply Shared Decision Making: discuss benefits and risks and obtain patient preference.

Choose based on safety (mainly) and efficacy.

Consider prior response and avoid previous side-effects.

Select an antipsychotic that does not worsen comorbidities (e.g. obesity, hyperlipidemia, diabetes, renal/liver failure, cardiovascular issues).

Consider drug-drug interactions, click for websites

Some antipsychotics require food intake (lurasidone ≥350 kcal, ziprasidone ≥500 kcal), other antipsychotics should be taken at least one hour before eating (quetiapine extended-release).

Liquids, rapidly dissolving tablets, long-half life facilitate adherence

Sedative effects can be useful in agitated or insomniac patients

Think ahead: E.g. if long-acting injectable (LAI) is planned for relapse prevention, choose oral antipsychotic which is also available as LAI

Consider drug availability in your country

Consider recommendations for patient subgroups in Section "Special Situations"

Offer CBT for psychosis to all patients

Use supportive therapy where CBT is unavailable

Offer CBT for psychosis to all patients

Use supportive therapy where CBT is unavailable

On average daily doses higher than 5mg/day risperidone equivalent are not more efficacious than lower doses

Use target doses suggested by the International Consensus Study of Antipsychotic Dosing. For tools and references see notes

On average daily doses higher than 5mg/day risperidone equivalent are not more efficacious than lower doses

Use target doses suggested by the International Consensus Study of Antipsychotic Dosing. For tools and references see notes

Gradual increase "Start low, go slow, but go", unless there is urgency

Some drugs can be immediately given in a full dose

Some drugs, e.g. iloperidone, quetiapine immediate release, risperidone, clozapine, require slow increase, mainly to avoid postural hypotension

Gradual increase "Start low, go slow, but go", unless there is urgency

Some drugs can be immediately given in a full dose

Some drugs, e.g. iloperidone, quetiapine immediate release, risperidone, clozapine, require slow increase, mainly to avoid postural hypotension

Drugs with longer half-time need to be given less frequently, but it takes longer to reach steady-state plasma-levels

It takes ~ 5 half lifes to reach steady state. Thus, if half life of ~ 24 hours as it is the case for many antipsychotics -> 5 days

Once daily dosing at bedtime is often possible. Such a simple regimen may enhance adherence and reduce side-effects (patients "sleep over" plasma-level peak)

Drugs with longer half-time need to be given less frequently, but it takes longer to reach steady-state plasma-levels

It takes ~ 5 half lifes to reach steady state. Thus, if half life of ~ 24 hours as it is the case for many antipsychotics -> 5 days

Once daily dosing at bedtime is often possible. Such a simple regimen may enhance adherence and reduce side-effects (patients "sleep over" plasma-level peak)

Do not consider a major change in treatment until 2-4 weeks of full treatment dose

Adherence?

• ask patient/relatives
• pill count
• plasma levels
• rule out with liquid drugs or long-acting injectable

Low plasma level despite sufficient dose?

• Drug-drug interactions?
• Low absorption?
• CYP ultrarapid metabolizer?
• Smoking reduces olanzapine and clozapine plasma levels via CYP1A2 induction

Parkinsonism symptoms mimicking negative symptoms or akathisia agitation?

Substance abuse counteracting response?

Life event (external stressor)?

Do not consider a major change in treatment until 2-4 weeks of full treatment dose

Adherence?

• ask patient/relatives
• pill count
• plasma levels
• rule out with liquid drugs or long-acting injectable

Low plasma level despite sufficient dose?

• Drug-drug interactions?
• Low absorption?
• CYP ultrarapid metabolizer?
• Smoking reduces olanzapine and clozapine plasma levels via CYP1A2 induction

Parkinsonism symptoms mimicking negative symptoms or akathisia agitation?

Substance abuse counteracting response?

Life event (external stressor)?

Aim for at least 80% intake

Long-acting injectable

Oral antipsychotic with long half-life

Simplify treatment e.g. aim for monotherapy at night

Liquids or rapidly dissolving tablets (inpatients)

Aim for at least 80% intake

Long-acting injectable

Oral antipsychotic with long half-life

Simplify treatment e.g. aim for monotherapy at night

Liquids or rapidly dissolving tablets (inpatients)

Increase dose beyond maximum effective doses only if plasma level is low despite adherence

Switch to a different antipsychotic considering efficacy differences and choose a different receptor binding profile.

No good evidence for augmentation strategies (see strategies for treatment resistance).

Increase dose beyond maximum effective doses only if plasma level is low despite adherence

Switch to a different antipsychotic considering efficacy differences and choose a different receptor binding profile.

No good evidence for augmentation strategies (see strategies for treatment resistance).

If necessary (e.g. severe side-effects) stopping the first antipsychotic and immediately starting the second is possible for most antipsychotics ('stop and start')

Usually 'cross-tapering' or 'overlap and taper' strategies are used. However consider to take more time if switching from a sedating antipsychotic to a non-sedating one (SGAs with 'done' as an ending) or to an antipsychotic with a long half-life which needs time to build up the plasma level (e.g. aripiprazole, brexpiprazole, cariprazine).

Aim for equivalent doses of the initial and subsequent antipsychotic.

If necessary (e.g. severe side-effects) stopping the first antipsychotic and immediately starting the second is possible for most antipsychotics ('stop and start')

Usually 'cross-tapering' or 'overlap and taper' strategies are used. However consider to take more time if switching from a sedating antipsychotic to a non-sedating one (SGAs with 'done' as an ending) or to an antipsychotic with a long half-life which needs time to build up the plasma level (e.g. aripiprazole, brexpiprazole, cariprazine).

Aim for equivalent doses of the initial and subsequent antipsychotic.

Liquid or rapidly dissolving medication can be useful, e.g. in inpatients

Simplify the regimen, reduce polypharmacy, once daily intake at night, if possible

If medications have a long half-life (e.g. aripiprazole, cariprazine) missing a dose is less important

LAIs may already be used in acutely ill patients if tolerability of the oral form has been confirmed

LAIs in relapse prevention

Liquid or rapidly dissolving medication can be useful, e.g. in inpatients

Simplify the regimen, reduce polypharmacy, once daily intake at night, if possible

If medications have a long half-life (e.g. aripiprazole, cariprazine) missing a dose is less important

LAIs may already be used in acutely ill patients if tolerability of the oral form has been confirmed

LAIs in relapse prevention

Patient psychoeducation

Family psychoeducation/interventions

Patient psychoeducation

Family psychoeducation/interventions

Need based psychotherapeutic approaches such as cognitive behavioral approaches, supportive therapy, family interventions.

Short-term, intermittent use of antipsychotics for psychotic symptoms only if CBT is ineffective

Need based psychotherapeutic approaches such as cognitive behavioral approaches, supportive therapy, family interventions.

Short-term, intermittent use of antipsychotics for psychotic symptoms only if CBT is ineffective

Prioritize de-escalation techniques

Multiple drugs (benzodiazepines, antipsychotics, antihistaminergics) and formulations (oral, rapidly dissolving tablets, inhalants, short-acting parenteral) exist

Use short-acting parenteral drugs only if oral administration is not feasible

Intramuscular haloperidol and lorazepam monotherapy are less efficacious than haloperidol combined with promethazine

Do not use benzodiazepines long-term they are associated with mortality

Follow SMPCs and follow regulations of your country

Prioritize de-escalation techniques

Multiple drugs (benzodiazepines, antipsychotics, antihistaminergics) and formulations (oral, rapidly dissolving tablets, inhalants, short-acting parenteral) exist

Use short-acting parenteral drugs only if oral administration is not feasible

Intramuscular haloperidol and lorazepam monotherapy are less efficacious than haloperidol combined with promethazine

Do not use benzodiazepines long-term they are associated with mortality

Follow SMPCs and follow regulations of your country

Consider clozapine

Consider clozapine

Antipsychotics with few side-effects and at low doses (~50% regular adult dose)

Coordinated specialty care for early psychosis patients

Antipsychotics with few side-effects and at low doses (~50% regular adult dose)

Coordinated specialty care for early psychosis patients

Antipsychotics with few side-effects and low doses (children 40%, adolescents 70% adult dose)

Escalations to antipsychotics with more side effects may be necessary if less harmful ones are ineffective.

Some specific antipsychotics can be prescribed for children and adolescents according to official licensing guidelines.

Antipsychotics with few side-effects and low doses (children 40%, adolescents 70% adult dose)

Escalations to antipsychotics with more side effects may be necessary if less harmful ones are ineffective.

Some specific antipsychotics can be prescribed for children and adolescents according to official licensing guidelines.

Generally uses antipsychotics with few side-effects and avoid antipsychotics which aggravate physical comorbidities

Low doses (~50% of adult dose)

Generally uses antipsychotics with few side-effects and avoid antipsychotics which aggravate physical comorbidities

Low doses (~50% of adult dose)

Use 10% lower doses

Consider gender specific side-effects such as dysmenorrhea and galactorrhea in drug choice

In long-term treatment, consider increased risk for breast cancer being associated with prolactin-increasing antipsychotics

If prolactin-increasing antipsychotics are used, prolactin should be monitored and lowered if too high, breast cancer screening should be routinely applied, and modifiable and nonmodifiable risk factors for breast should be considered in individual, shared decisions

Use 10% lower doses

Consider gender specific side-effects such as dysmenorrhea and galactorrhea in drug choice

In long-term treatment, consider increased risk for breast cancer being associated with prolactin-increasing antipsychotics

If prolactin-increasing antipsychotics are used, prolactin should be monitored and lowered if too high, breast cancer screening should be routinely applied, and modifiable and nonmodifiable risk factors for breast should be considered in individual, shared decisions

Individual decision weighing the risk for unborn child and mother stemming from schizophrenia and from antipsychotic side-effects, but usually protection from relapse will outweigh the risks

Aim for monotherapy and low doses

Similar considerations apply to breast feeding, because small amounts of antipsychotics pass into breast milk

Search expert advice about which antipsychotic is the most suitable

Individual decision weighing the risk for unborn child and mother stemming from schizophrenia and from antipsychotic side-effects, but usually protection from relapse will outweigh the risks

Aim for monotherapy and low doses

Similar considerations apply to breast feeding, because small amounts of antipsychotics pass into breast milk

Search expert advice about which antipsychotic is the most suitable

Follow SMPCs because certain antipsychotics are contraindicated in such patients

Dose adjustments may be necessary

Consider plasma-levels

In patients with renal dysfunction consider antipsychotics mainly metabolized via the liver (e.g. olanzapine, quetiapine, aripiprazole, clozapine)

In patients with liver dysfunction consider drugs mainly or at least in part excreted unchanged via the kidneys (e.g. amisulpride, paliperidone)

Monitor kidney/liver function

Follow SMPCs because certain antipsychotics are contraindicated in such patients

Dose adjustments may be necessary

Consider plasma-levels

In patients with renal dysfunction consider antipsychotics mainly metabolized via the liver (e.g. olanzapine, quetiapine, aripiprazole, clozapine)

In patients with liver dysfunction consider drugs mainly or at least in part excreted unchanged via the kidneys (e.g. amisulpride, paliperidone)

Monitor kidney/liver function

Antipsychotics with few side-effects, starting with low doses (e.g. 25% lower than regular doses)

Antipsychotics with few side-effects, starting with low doses (e.g. 25% lower than regular doses)

When treating negative symptoms in acutely ill schizophrenia patients, first rule out secondary causes:

a) Positive Symptoms: Treat with antipsychotics as these may resolve negative symptoms secondary to delusions or hallucinations.

b) Extrapyramidal Side Effects (EPS): Address EPS (e.g., switch antipsychotic) as these can mimic negative symptoms like reduced facial expression.

c) Depressive Symptoms: Treat depressive symptoms, which can be difficult to distinguish from negative symptoms

Only amisulpride, clozapine, olanzapine, risperidone and zotepine have been shown to be more efficacious for secondary negative symptoms than haloperidol in acutely ill patients with positive symptoms

For persistent (primary) negative symptoms consider:

a) Cariprazine

b) Low-dose amisulpride (50-300mg/day)

c) Adding an antidepressant

d) Non-invasive brain stimulation

Effective psychotherapeutic interventions:

• Social skills training
• Cognitive behaviour therapy
• Exercise

When treating negative symptoms in acutely ill schizophrenia patients, first rule out secondary causes:

a) Positive Symptoms: Treat with antipsychotics as these may resolve negative symptoms secondary to delusions or hallucinations.

b) Extrapyramidal Side Effects (EPS): Address EPS (e.g., switch antipsychotic) as these can mimic negative symptoms like reduced facial expression.

c) Depressive Symptoms: Treat depressive symptoms, which can be difficult to distinguish from negative symptoms

Only amisulpride, clozapine, olanzapine, risperidone and zotepine have been shown to be more efficacious for secondary negative symptoms than haloperidol in acutely ill patients with positive symptoms

For persistent (primary) negative symptoms consider:

a) Cariprazine

b) Low-dose amisulpride (50-300mg/day)

c) Adding an antidepressant

d) Non-invasive brain stimulation

Effective psychotherapeutic interventions:

• Social skills training
• Cognitive behaviour therapy
• Exercise

Do not immediately add an antidepressant because antipsychotics alone can improve psychosis associated depression

In particular first-generation dopamine antagonists such as haloperidol may produce "antipsychotic induced dysphoria"

Consider dose reduction or switch if antipsychotic is suspected to cause depression ("antipsychotic-induced depression"); add antidepressant if b) depression persists or c) in postpsychotic depression. The risk of worsening psychosis is low.

Cognitive behavioural therapy

Do not immediately add an antidepressant because antipsychotics alone can improve psychosis associated depression

In particular first-generation dopamine antagonists such as haloperidol may produce "antipsychotic induced dysphoria"

Consider dose reduction or switch if antipsychotic is suspected to cause depression ("antipsychotic-induced depression"); add antidepressant if b) depression persists or c) in postpsychotic depression. The risk of worsening psychosis is low.

Cognitive behavioural therapy

Treat manic symptoms with antipsychotics, which also act as mood stabilizers. Only add mood stabilizer if manic symptoms persist.

Treat manic symptoms with antipsychotics, which also act as mood stabilizers. Only add mood stabilizer if manic symptoms persist.

The condition is severe and, in extreme cases, can lead to death. Conditions mimicking catatonia might also lead to death. Pay attention to the specific symptoms needed for diagnosis and differential diagnosis.

Benzodiazepines

ECT (in particular in severe cases)

The condition is severe and, in extreme cases, can lead to death. Conditions mimicking catatonia might also lead to death. Pay attention to the specific symptoms needed for diagnosis and differential diagnosis.

Benzodiazepines

ECT (in particular in severe cases)

As long as symptoms of schizophrenia and mania and/or depression are present at the same time (as it is part of the DSM-5 definition), antipsychotics are the main treatment and the principles of this guideline may be followed

As long as symptoms of schizophrenia and mania and/or depression are present at the same time (as it is part of the DSM-5 definition), antipsychotics are the main treatment and the principles of this guideline may be followed

Chose second-generation antipsychotic with a favorable side-effect profile

Typically for a prolonged duration, potentially years

Cognitive Behavioural Therapy for Psychosis

Supportive psychotherapy

Chose second-generation antipsychotic with a favorable side-effect profile

Typically for a prolonged duration, potentially years

Cognitive Behavioural Therapy for Psychosis

Supportive psychotherapy

As non-adherence is often a problem consider long-acting injectables (LAI)

Avoid first-generation dopamine blockers such as haloperidol

Employ established psychotherapies for substance use disorders

Refer to specialized double-diagnosis service, if available

As non-adherence is often a problem consider long-acting injectables (LAI)

Avoid first-generation dopamine blockers such as haloperidol

Employ established psychotherapies for substance use disorders

Refer to specialized double-diagnosis service, if available

Cognitive remediation

Aerobic Exercise

Avoid high-potency first-generation antipsychotics such as haloperidol at high doses and clozapine (anticholinergic and sedating)

Avoid anticholinergics and sedative medication (e.g. benzodiazepines)

We consider other interventions more experimental

Cognitive remediation

Aerobic Exercise

Avoid high-potency first-generation antipsychotics such as haloperidol at high doses and clozapine (anticholinergic and sedating)

Avoid anticholinergics and sedative medication (e.g. benzodiazepines)

We consider other interventions more experimental

OCD symptoms can be part of schizophrenia or side-effects of antipsychotics. Antipsychotics with a serotonergic mechanism, in particular clozapine, but also e.g. risperidone, olanzapine quetiapine seem to have a higher risk than partial dopamine agonists or amisulpride.

Whether the OCD symptoms were present before or after starting and antipsychotic helps in understanding their cause

If OCD symptoms are part of schizophrenia, use SSRIs and CBT

If OCD symptoms are side-effects of medication, consider switching to antipsychotics with a lower risk of inducing obsessive-compulsive symptoms

OCD symptoms can be part of schizophrenia or side-effects of antipsychotics. Antipsychotics with a serotonergic mechanism, in particular clozapine, but also e.g. risperidone, olanzapine quetiapine seem to have a higher risk than partial dopamine agonists or amisulpride.

Whether the OCD symptoms were present before or after starting and antipsychotic helps in understanding their cause

If OCD symptoms are part of schizophrenia, use SSRIs and CBT

If OCD symptoms are side-effects of medication, consider switching to antipsychotics with a lower risk of inducing obsessive-compulsive symptoms

Clozapine

Clozapine

Definitions:

• Treatment-resistance: Non-response to at least 2 antipsychotics at sufficient dose and for 6 weeks each
• Non-response, narrow criterion: Less than minimally improved, corresponding to ≤ 25% PANSS/BPRS total score reduction
• Non-response, broader criterion: Less than much improved corresponding to ≤ 50% PANSS/BPRS total score reduction
• Remission: 8 positive, negative and disorganisation items maximally mild for at least 6 months

Definitions:

• Treatment-resistance: Non-response to at least 2 antipsychotics at sufficient dose and for 6 weeks each
• Non-response, narrow criterion: Less than minimally improved, corresponding to ≤ 25% PANSS/BPRS total score reduction
• Non-response, broader criterion: Less than much improved corresponding to ≤ 50% PANSS/BPRS total score reduction
• Remission: 8 positive, negative and disorganisation items maximally mild for at least 6 months

After 2 failed trials with dose ≥ 600mg chlorpromazine equivalent/day and ≥ 6 weeks duration, one of them olanzapine, use clozapine

Increase clozapine by at most 25–50 mg/day to target dose of 300–450 mg/day

If no response, target plasma levels ≥ 350 ng/mL (clozapine alone, not combined with norclozapine)

Clozapine:Norclozapine ratio < 0.5 suggests poor adherence or rapid metabolism.

Further dose increases not more than 100 mg once/twice weekly.

Smoking reduces clozapine plasma-levels by induction of CYP1A2. If patients stop smoking, plasma-levels increase and side-effects can occur.

In some countries only special prescribers are allowed to prescribe clozapine.

After 2 failed trials with dose ≥ 600mg chlorpromazine equivalent/day and ≥ 6 weeks duration, one of them olanzapine, use clozapine

Increase clozapine by at most 25–50 mg/day to target dose of 300–450 mg/day

If no response, target plasma levels ≥ 350 ng/mL (clozapine alone, not combined with norclozapine)

Clozapine:Norclozapine ratio < 0.5 suggests poor adherence or rapid metabolism.

Further dose increases not more than 100 mg once/twice weekly.

Smoking reduces clozapine plasma-levels by induction of CYP1A2. If patients stop smoking, plasma-levels increase and side-effects can occur.

In some countries only special prescribers are allowed to prescribe clozapine.

The following side-effects need special attention:

1. Agranulocytosis (white blood cell count weekly for 18 weeks then monthly)
2. Myocarditis/cardiopathy
3. Constipation
4. Pneumonia
5. Tachycardia
6. Fever
7. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
8. Seizures (dose-related risk)
9. Venous Thromboembolism (VTE)

For other side-effects see Management of Side-Effects Section

The following side-effects need special attention:

1. Agranulocytosis (white blood cell count weekly for 18 weeks then monthly)
2. Myocarditis/cardiopathy
3. Constipation
4. Pneumonia
5. Tachycardia
6. Fever
7. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
8. Seizures (dose-related risk)
9. Venous Thromboembolism (VTE)

For other side-effects see Management of Side-Effects Section

Individualized decision. If the risk for relapse is greater than the risk of recurrent severe neutropenia, it may be tried. Check FDA recommendation in notes.

Individualized decision. If the risk for relapse is greater than the risk of recurrent severe neutropenia, it may be tried. Check FDA recommendation in notes.

1. Wait at least 3 months after complete recovery
2. Begin with ultra-slow titration: 6.25 mg every 4 days
3. After reaching 75 mg daily, increase to 6.25 mg every 3 days
4. After reaching 150 mg daily, increase to 6.25 mg every 2 days
5. Monitor with weekly CRP, troponin, NT-proBNP during titration
6. Avoid concomitant valproate and olanzapine when possible
7. Consider cardiac MRI before and after rechallenge

1. Wait at least 3 months after complete recovery
2. Begin with ultra-slow titration: 6.25 mg every 4 days
3. After reaching 75 mg daily, increase to 6.25 mg every 3 days
4. After reaching 150 mg daily, increase to 6.25 mg every 2 days
5. Monitor with weekly CRP, troponin, NT-proBNP during titration
6. Avoid concomitant valproate and olanzapine when possible
7. Consider cardiac MRI before and after rechallenge

• For one seizure: Reduce clozapine dose by 25-50%. Add anticonvulsant prophylaxis, such as sodium valproate or another suitable anticonvulsant.
• For repeated seizures: Discontinue clozapine. Reduce clozapine dose by 25-50%. Add sodium valproate or another anticonvulsant.
• Prophylaxis: If EEG shows propensity for seizures, augment with an anticonvulsant as prophylaxis. Consider using concomitant benzodiazepines (not IV) if needed during titration.

• For one seizure: Reduce clozapine dose by 25-50%. Add anticonvulsant prophylaxis, such as sodium valproate or another suitable anticonvulsant.
• For repeated seizures: Discontinue clozapine. Reduce clozapine dose by 25-50%. Add sodium valproate or another anticonvulsant.
• Prophylaxis: If EEG shows propensity for seizures, augment with an anticonvulsant as prophylaxis. Consider using concomitant benzodiazepines (not IV) if needed during titration.

• Recognize: Look for rash, fever, eosinophilia, systemic/liver involvement; consider RegiSCAR criteria.
• Manage: Discontinue clozapine & suspect co-meds immediately. Consider systemic corticosteroids.
• Rechallenge: Avoid clozapine rechallenge after confirmed DRESS due to recurrence risk.

• Recognize: Look for rash, fever, eosinophilia, systemic/liver involvement; consider RegiSCAR criteria.
• Manage: Discontinue clozapine & suspect co-meds immediately. Consider systemic corticosteroids.
• Rechallenge: Avoid clozapine rechallenge after confirmed DRESS due to recurrence risk.

There is no convincing evidence that combining antipsychotics is effective in treatment-resistant patients.

Combining antipsychotics with complementary receptor profiles at least has a theoretical rationale (e.g., combining clozapine, which has only 40% dopamine binding, with a selective dopamine antagonist or partial dopamine agonist).

If such a strategy is tried, it should be evaluated after a few weeks and stopped if it was not effective

There is no convincing evidence that combining antipsychotics is effective in treatment-resistant patients.

Combining antipsychotics with complementary receptor profiles at least has a theoretical rationale (e.g., combining clozapine, which has only 40% dopamine binding, with a selective dopamine antagonist or partial dopamine agonist).

If such a strategy is tried, it should be evaluated after a few weeks and stopped if it was not effective

No augmentation strategy can be recommended.

Exceptions are antidepressants for persistent negative symptoms or depression patient subgroups

Consider drug-drug interactions.

If augmentation is tried, it should be evaluated after a few weeks and stopped if it was not effective

No augmentation strategy can be recommended.

Exceptions are antidepressants for persistent negative symptoms or depression patient subgroups

Consider drug-drug interactions.

If augmentation is tried, it should be evaluated after a few weeks and stopped if it was not effective

Use Cognitive Behavioral Therapy for psychosis (CBTp)

Use Cognitive Behavioral Therapy for psychosis (CBTp)

Some evidence for low-frequency repetitive Transcranial Magnetic Stimulation (rTMS), applied over the temporal lobe, for persistent auditory hallucinations

Some evidence for high-frequency rTMS at 10/20 Hz, applied over the left dorsolateral prefrontal cortex for negative symptoms

Some evidence for low-frequency repetitive Transcranial Magnetic Stimulation (rTMS), applied over the temporal lobe, for persistent auditory hallucinations

Some evidence for high-frequency rTMS at 10/20 Hz, applied over the left dorsolateral prefrontal cortex for negative symptoms

ECT maybe used as a last resort for patients unresponsive to clozapine

If ECT was effective, consider maintenance ECT

ECT maybe used as a last resort for patients unresponsive to clozapine

If ECT was effective, consider maintenance ECT

Even among patients with a first-episode of schizophrenia only approximately 20% will not have a second one

To predict who they are is currently impossible

Thus, antipsychotic relapse prevention should be offered to all patients

Shared decision making discussing benefits and risks should be applied

Even among patients with a first-episode of schizophrenia only approximately 20% will not have a second one

To predict who they are is currently impossible

Thus, antipsychotic relapse prevention should be offered to all patients

Shared decision making discussing benefits and risks should be applied

Patients should be explained that their relapse and rehospitalization risk is ~ 2 times increased if they stop their antipsychotic, including first-episode patients, patients in remission and those who have been relapse free on antipsychotics for many years

Patients who have experienced multiple episodes may benefit from antipsychotics for long periods up to lifelong

First episode patients should receive antipsychotics for at least 1 year. They may want to find out whether they are among the 20% without a second episode without treatment

Decisions should be individual, shared between doctor and patient, and depend on the severity of the index episode, remaining symptoms, illness course, side-effects, the availability of family and/or psychosocial support, patients' employment situation and others

Patients should be explained that their relapse and rehospitalization risk is ~ 2 times increased if they stop their antipsychotic, including first-episode patients, patients in remission and those who have been relapse free on antipsychotics for many years

Patients who have experienced multiple episodes may benefit from antipsychotics for long periods up to lifelong

First episode patients should receive antipsychotics for at least 1 year. They may want to find out whether they are among the 20% without a second episode without treatment

Decisions should be individual, shared between doctor and patient, and depend on the severity of the index episode, remaining symptoms, illness course, side-effects, the availability of family and/or psychosocial support, patients' employment situation and others

Continue with the antipsychotic that was efficacious and well-tolerated during the acute phase

Consider the higher risk of tardive dyskinesia of first-generation-antipsychotics and significant weight gain with several second-generation antipsychotics

Continue with the antipsychotic that was efficacious and well-tolerated during the acute phase

Consider the higher risk of tardive dyskinesia of first-generation-antipsychotics and significant weight gain with several second-generation antipsychotics

Switch the antipsychotic rather than reduce the dose

Switch the antipsychotic rather than reduce the dose

Long-acting injectable (LAIs) are associated with lower relapse rates than oral antipsychotics

They can be offered to all patients in a shared-decision making process

They are particularly useful for patients with adherence problems

Selection criteria are similar to those for oral antipsychotics

Additional criteria are injection frequency (formulations between 1 week and 6 months are available, depending on country), necessity of initial oral supplementation or boostering, and injection site (gluteal or arm; intramuscular or subcutaneous)

Tolerability of the oral form of an antipsychotic should have been established.

Check the Severe Mental Illness Advisor (SMI) website, which provides multiple sources of practical information on LAI antipsychotics.

Long-acting injectable (LAIs) are associated with lower relapse rates than oral antipsychotics

They can be offered to all patients in a shared-decision making process

They are particularly useful for patients with adherence problems

Selection criteria are similar to those for oral antipsychotics

Additional criteria are injection frequency (formulations between 1 week and 6 months are available, depending on country), necessity of initial oral supplementation or boostering, and injection site (gluteal or arm; intramuscular or subcutaneous)

Tolerability of the oral form of an antipsychotic should have been established.

Check the Severe Mental Illness Advisor (SMI) website, which provides multiple sources of practical information on LAI antipsychotics.

It is safest to stay on a standard dose (approximately 5 mg/day risperidone equivalent); if patients have responded to a lower dose in the acute phase, it should be sufficient ("what made you well, keeps you well").

On average higher doses are associated with more side-effects but no additional efficacy