Schizophrenia – CJP

1 In adolescents presenting with problem behaviours, consider schizophrenia in the differential diagnosis.

Differential Diagnosis of Psychosis – GASPP
  • General medical condition: head tumor/trauma, dementia/delirium, metabolic/infection/stroke, temporal lobe epilepsy
  • Affective disorders: bipolar / depression with psychotic features
  • Substance induced: intoxication/withdrawal, toxins
  • Psychotic disorders : schizophrenia, schizophreniform, brief psychotic, schizoaffective, shared psychotic, delusional disorder
  • Personality disorders: schizotypal, schizoid, borderline, paranoid, OBCP

DSM-IV-TR Diagnostic Criteria for Schizophrenia
  1. characteristic symptoms (active phase): ≥2 of the following, each present for a significant portion of time during a 1-mo period (or less if successfully treated)
    • delusions
    • hallucinations
    • disorganized speech (e.g. frequent derailment or incoherence)
    • grossly disorganized or catatonic behaviour
    • negative symptoms [e.g. affective flattening, alogia (inability to speak), or avolition (inability to initiate and persist in goal-directed activities)]
    • Note: only 1 “A” symptom is required if delusions are bizarre or hallucinations consist of a voice keeping a running commentary on the person’s behaviour or thoughts, or 2 or more voices conversing with each other
  2. social/occupational dysfunction: ≥1 major areas of functioning (work, interpersonal relations, self-care) markedly below the level achieved prior to the onset of symptoms
  3. continuous signs of disturbance for ≥6 mo, including ≥1 mo of active phase symptoms; may include prodromal or residual phases
  4. schizoaffective and mood disorders excluded
  5. the disturbance is not due to the direct physiological effects of a substance or a GMC
  6. if history of pervasive developmental disorder, additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least 1 mo
  1. paranoid
    • preoccupation with delusions (typically persecutory or grandiose) or frequent auditory hallucinations
    • relative preservation of cognitive functioning and affect; onset tends to be later in life; believed to have the best prognosis
  2. catatonic
    • at least two of: motor immobility (catalepsy or stupor); excessive motor activity (purposeless); extreme negativism (resistance to instructions/attempts to be moved) or mutism; peculiar voluntary movement (posturing, stereotyped movements, prominent mannerisms); echolalia or echopraxia (copying another’s speech or movement)
  3. disorganized
    • disorganized speech and behaviour; flat or inappropriate affect
    • poor premorbid personality, early and insidious onset, and continuous course without significant remissions
  4. undifferentiated
    • meets criteria for schizophrenia, but does not fall into the 3 previous subtypes
  5. residual
    • no longer have prominent delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behaviour
    • continuing evidence of residual illness such as negative symptoms or attenuated symptoms of criteria A

Schizophreniform Disorder

diagnosis: criteria A, D and E of schizophrenia are met; an episode of the disorder lasts from 1-6 mo. If the symptoms have extended past 6 mo the diagnosis becomes schizophrenia

treatment: similar to acute schizophrenia

prognosis: better than schizophrenia; begins and ends more abruptly; good pre- and postmorbid function

Brief Psychotic Disorder

diagnosis: acute psychosis (presence of 1 or more positive symptoms in criteria  A 1-4 of schizophrenia) lasting from 1 day to 1 mo, with eventual full return to premorbid level of functioning

can occur after a stressful event or postpartum

treatment: secure environment, antipsychotics, anxiolytics

prognosis: good, self-limiting, should return to pre-morbid function in about 1 mo

Schizoaffective Disorder

A. uninterrupted period of illness during which there is either a MDE, manic episode, or a mixed episode concurrent with symptoms meeting criteria A for schizophrenia

B. in the same period, delusions or hallucinations for ≥2 wk in the absence of prominent mood symptoms

C. symptoms that meet criteria for a mood episode are present for a substantial portion of total duration of active and residual periods of the illness

D. the disturbance is not due to the direct physiological effects of a substance or GMC

treatment: antipsychotics, mood stabilizers, antidepressants

prognosis: between that of schizophrenia and of mood disorder

Delusional Disorder

A. non-bizarre delusions for ≥1 mo

B. criterion A for schizophrenia has never been met (though patient may have tactile or olfactory hallucinations if they are related to the delusional theme)

C. functioning not markedly impaired; behaviour not obviously odd or bizarre

D. if mood episodes occur concurrently with delusions, total duration has been brief relative to

duration of the delusional periods

E. the disturbance is not due to the direct physiological effects of a substance or GMC

subtypes: erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified

treatment: psychotherapy, antipsychotics, antidepressants

prognosis: chronic, unremitting course but high level of functioning

Shared Psychotic Disorder (Folie à Deux)

diagnosis: delusion that develops in an individual who is in a close relationship with another person who already has a psychotic disorder with prominent delusions; the delusion is similar in content to that of the other person

treatment: separation of the two people results in the disappearance of the delusion in the healthier member; antipsychotics may play a role

prognosis: good

2 In “apparently” stable patients with schizophrenia (e.g., those who are not floridly psychotic), provide regular or periodic assessment in a structured fashion e.g.- positive and negative symptoms, the performance of activities of daily living, and the level of social functioning at each visit; – seeking collateral information from family members and other caregivers to develop a more complete assessment of symptoms and functional status; – competency to accept or refuse treatment , and document specifically; – suicidal and homicidal ideation, as well as the risk for violence; – medication compliance and side effects

  1. S/Sx of illness and functional impairment should be carefully evaluated and ddx made.
    • Among illnesses with psychosis as a clinical feature, the diagnosis of schizophrenia has significant implications for prognosis. A
  2. Suicidal and aggressive thinking and behaviour should be regularly assessed.
    • Patients with schizophrenia have increased risk of suicide and aggression. A
  3. Regular assessment of substance use and abuse is necessary.
    • Substance abuse is common in patients with schizophrenia. A
  4. Neuropsychological testing is suggested in patients with first-episode psychosis and those with poor response to treatment.
    • Schizophrenia is associated with mild but significant cognitive impairment, which is associated with poor functional recovery. B
  5. Symptoms, level of function, and factors associated with poor treatment adherence and relapse should be regularly assessed.
    • Schizophrenia is frequently characterized by exacerbations of symptoms and periods of acute relapse. A
  6. Clinical features suggestive of chromosome 22q11 syndrome should be evaluated in patients with schizophrenia and laboratory testing obtained when indicated.
    • Chromosome 22q11 deletion is associated with schizophrenia. B
  7. CT/MRI at illness onset and in patients with refractory illness should be done.
    • Patients with schizophrenia have an increased prevalence of structural brain abnormalities. B
  8. Regular clinical and laboratory monitoring for movement disorders, obesity, diabetes, hyperlipidemia and sexual dysfunction indicated in patients with schizophrenia.
    • Patients with schizophrenia have reduced life expectancy; the combination of illness and the effects of antipsychotic treatment place patients at risk of movement disorders, obesity, diabetes, hyperlipidemia, and sexual dysfunction. A


  • Positive: hallucinations and delusions
  • Negative: flat or blunted affect, poverty of thought or thought content, and avolition
  • Disorganization: thought disorder, inappropriate affect, and disorganized behaviour
  • Mood: anxiety or depression, particularly in relation to the psychotic symptoms
  • Suicide, aggression, or impulsivity: any risk for suicide or violence has implications for where the patient should be assessed and treated
  • the time of onset or exacerbation of symptoms and the context and possible precipitating factors
Level of function Social
  • Collateral information from caregivers and (or) a home visit may be very helpful in this assessment
  • Living situation: including housing, finances, social supports, ADLs, ability to perform basic self-care
  • social activity (extent of social relationship), school
  • Occupational or vocational – the ability to learn and work
  • The frequency of hospitalization due to relapses
Substance use or abuse
  • Inquiry:Substance use  in relation to the onset and persistence of psychotic and associated symptoms
  • Toxicology screen
  • Family history of psychosis
  • Clinical screening for chromosome 22q11 deletion syndrome (with testing as indicated clinically)
Functional inquiry:
  • Women: menstruation, libido, galactorrhea
  • Men: libido, erectile and ejaculatory function
ROS: general, Inquiry about cataract
  • cognitive function, based on data from all sources of information, in which positive and negative findings should be documented, since they may change over time
  • Insight: awareness of the significance of illness, attitude toward treatment and restoring health, medication adherence
PE: VS & neurologic examination and Ocular exam
BMI & Waist circumference (Before initiating a new antipsychotic, then monthly for 6 months)
Laboratory tests:
  • CBC, Electrolytes, Renal function tests, Liver function tests, Thyroid function tests
  • Fasting plasma glucose, Lipid panel
  • Syphilis test, Hepatitis or HIV tests if indicated
  • Where clinically indicated: prolactin level
  • ECG – QTc indicated when affected by multiple medications
Structural brain abnormalities – CT or MRI as indicated clinically
Extrapyramidal symptoms and signs
  • Parkinsonism (bradykinesia, rigidity, tremor), Dystonia, Dyskinesia, Akathisia

Stable Phase

Patients in the stable phase who have good functional recovery and are in a stable living situation should be assessed by a physician at least every 3 months.

More frequent  if pt have

  • poor functional recovery
  • associated conditions such as substance use or abuse,
  • have limited social support, are changing medications,
  • are initiating a new psychosocial intervention, or
  • are experiencing stressful life events.
  • Persistent symptoms (positive, negative, and comorbid) are not always associated with overt patient distress but often limit functional recovery

3 In all patients presenting with psychotic symptoms, inquire about substance use and abuse.

4 Consider the possibility of substance abuse and look for it in patients with schizophrenia, as this is a population at risk.

5 In patients with schizophrenia, assess and treat substance abuse appropriately.

6 In decompensating patients with schizophrenia, determine: – if substance abuse is contributory. – the role of medication compliance and side-effect problems. – if psychosocial supports have changed.

  1. Antipsychotic medication for the treatment of a first-episode psychosis should be continued for a minimum of 2 years following first recovery of symptoms.
  2. There is evidence to suggest that the risk of relapse is greatest in the first 5 years. 
  3. Long-acting injectable antipsychotic medication should be considered for those patients who show poor medication adherence.
    • The nature of nonadherence makes it hard to conduct RCTs in this population. 
  4. Treatment nonresponse to adequate trials of antipsychotics from 2 different classes is an indication for a trial of clozapine.
    • RCTs and metaanalyses support the superiority of clozapine over other antipsychotics for treatment nonresponse. 
  5. Persistent aggressivity may be helped by a trial of clozapine.
    • Case series support the benefit of clozapine for persistent aggressivity.
  6. Persistent suicidal thoughts or behaviours are an indication that clozapine should be considered.
    • One randomized open-label study has shown significant reduction in suicidality, compared with active control treatment. 
  7. A major depressive episode in the stable phase of schizophrenia is an indication for a trial of an antidepressant.
    • Results of some RCTs comparing antidepressants with placebo have been positive. 

7 Diagnose and treat serious complications/side effects of antipsychotic medications (e.g., neuroleptic malignant syndrome, tardive dyskinesia).

Extrapyramidal Side Effects (↑ w/ FGAs)
  • Acute reactions occurring in the first days or weeks oftreatment include:
    • dystonia, parkinsonism (akinesia or bradykinesia, tremor, and rigidity), and akathisia.
  • Chronic side effects, some irreversible and appearing months or years after treatment, include
    • TD and tardive dystonia. 
  • Risks of neurologic side effects from SGAs are minimal, but subtle signs of tremor, rigidity, and akathisia still can be detected and could be easily mistaken for anxiety, agitation, or negative symptoms.
  • Higher dosages of risperidone > olanzapine are associated with a higher risk of EPSEs
  • If neurologic symptoms are detected,
    • a dosage reduction of the antipsychotic should be tried, or switch to another SGA.
    • A benzodiazepine or beta blocker can be prescribed for akathisia if a dosage reduction is insufficient.
    • Anticholinergic medication is usually not recommended with the use of SGAs.
  • Clozapine exhibits the lowest risk and may improve existing TD.
  • Symptoms are not alleviated by antiparkinsonian medication and may worsen. A switch to an SGA is recommended, and a clozapine trial should be considered in the presence of persistent symptoms of TD

Neuroleptic Dysphoria (FGA > SGAs)

Includes various subtle, unpleasant, subjective changes in arousal, mood, thinking, and motivation. It is associated with noncompliance, substance abuse, poor clinical outcome, increased suicidality, and compromised quality of life.

Neuroleptic Malignant Syndrome (medical emergency with a high mortality rate)
  • A rare and severe condition with symptoms of:
    • rigidity, tachycardia, hyperthermia, autonomic dysfunctions, and altered consciousness
    • elevated levels of serum creatine kinase
  • It can occur with any antipsychotic agent, at any dosage, and any time.
  • Risk factors include:
    • young age, male sex, neurologic disabilities, dehydration, exhaustion, agitation
    • rapid or parenteral administration of antipsychotic.
  • This side effect is potentially fatal if not managed promptly.
  • Antipsychotic medication should be stopped and supportive therapy instituted.
  • Agonists such as dantrolene, bromocriptine, or amantadine may improve symptoms

Weight Gain and Abdominal Obesity
  1. Clozapine and olanzapine > risperidone and quetiapine
  2. Lean persons & young patients seem to be particularly vulnerable to dramatic weight gain
  3. Combinations with some psychotropic drugs such as lithium, valproate, and some antidepressants may significantly worsen the weight-gain
  4. Preventive lifestyle strategies should be encouraged
    • Benefits of physical activities and good nutrition habits should be emphasized both to the patient and to his or
      her family.
  5. If prevention is insufficient to limit wt gain, consider change to an antipsychotic with a lower weight-gain liability
Impairment in Glucose Regulation and Diabetes
  • Glucose abn reported with atypical antipsychotic treatment: insulin resistance, hyperglycaemia, exacerbation of DM1/2 & DKA. In Canada, all SGAs carry a warning for potential glucose abnormalities.
  • Second-generation antipsychotics may elevate lipids. clozapine and olanzapine can be associated with hyperlipidemia.
QT Prolongation
  • Prolongation of the QT interval is an ECG abnormality that can lead to torsades de pointes, arrhythmia, syncope, ventricular fibrillation, and sudden death.
  • Risk seems to be greater with QTc values over 500 ms.
Endocrine and Sexual Side Effects (especially with FGAs)
  • In women, changes in libido, delayed or absent orgasm, menstrual changes, or galactorrhea
  • in men, changes in libido, erectile or ejaculatory troubles, or galactorrhea
  • Hyperprolactinemia ↓ gonadal hormones – Prolonged hyperprolactinemia and decreased hormonal levels may increase risk of osteopenia, osteoporosis, and impaired reproductive function in women
  • SGAs show a lesser degree of elevation of prolactin levels, with the exception of risperidone, which is frequently associated with marked and sustained hyperprolactinemia, particularly if higher dosages are used
  • Quetiapine and clozapine are considered prolactin-sparing agents
    • birth control for women changing from an FGA or risperidone to a prolactin-sparing agent, since fertility level may be unexpectedly restored
Cognitive Side Effects and Sedation
  • FGAs induce sedation & ubjective dulling effect.
  • SGAs improves cognitive performance (not FGAs). Significant sedation may still occur with clozapine > olanzapine and quetiapine > risperidone (insomnia sometimes).
  • High risperidone dosages > high olanzapine dosages increase EPSEs, which in turn may impair cognitive performance.

Clozapine Side Effect Profile
  • Serious & fatal s/e:
    • agranulocytosis (0.5% to 2.0%) – ↑ first 6mo, qwk CBC to ensure that (WBC >3000) & neutrophils >1500
    • seizures (2% to 3%) – at ↑ dose
    • myocarditis and cardiomyopathy (rare).
  • Also associated with
    • significant weight gain and glucose and lipid disturbances.
    • sialorrhea
    • significant sedation, hypotension, tachycardia,
    • significant anticholinergic side effects such as
      • constipation, dry mouth, blurred vision, gastroparesis, and enuresis.
  • It does not elevate prolactin levels or induce EPSEs

8 Include psychosocial supports (e.g., housing, family support, disability issues, vocational rehabilitation) as part of the treatment plan for patients with schizophrenia.

Management of Schizophrenia
  • biological
    • acute treatment and maintenance with antipsychotics ± anticonvulsants ± anxiolytics
  • psychosocial
    1. psychotherapy (individual, family, group): supportive, CBT.
    2. assertive community treatment (ACT): mobile mental health teams that provide individualized treatment in the community and help patients with medication adherence, basic living skills, social support, job placements, and community resources
    3. Social skills training, employment programs, disability benefits
    4. housing (group home, boarding home, transitional home)

Good Prognostic Factors
  • Acute & Later age at onset
  • Shorter duration of prodrome
  • Female gender
  • Good cognitive functioning & premorbid functioning
  • No family history
  • Presence of affective symptoms
  • Absence of structural brain abnormalities
  • Good response to drugs
  • Good support system

Adherence is promoted by
  1. a good relationship with the clinician
    • Listening and attending to the patient’s concerns develops empathy, rapport, and a good therapeutic relationship. As well, it can improve engagement and adherence to treatment.
  2. patient and family knowledge about the illness
    • share plans for early recognition of relapse and crisis response with patient, family, and caregivers
  3. understanding the risk of nonadherence to medication (up to 90% of relapse within 1 year)
  4. low medication side effects
Nonadherence is associated with
  1. denial of illness and stigma
  2. distressing side effects
  3. complicated dosage schedules
  4. substance abuse,
  5. problems with access to treatment
  6. financial obstacles to receiving medication

  • Psychoeducation is an important intervention that needs to be accompanied by training in practical illness management strategies to achieve medication treatment adherence and to prevent relapse.
    • Psychoeducation can improve knowledge about illness, but there are equivocal findings that it increases treatment adherence unless there are also motivational enhancement and behavioural strategies for taking medication as prescribed. 
Vocational interventions
  • A wide range of possibilities should be considered for patients who are able to work, including volunteer work, supported, or transitional employment.
    • Individuals who suffer from schizophrenia have historically had low rates of employment; meaningful vocational activity, including paid employment, can be positive for individuals’ psychological health and quality of life. 
  • For many patients it is important to formulate goals for competitive paid employment and, in general, supported employment programs appear to offer the best approach to meeting such goals.
    • Supported employment approaches result in greater success in obtaining competitive paid employment. 
Skills training
  • Social skills training should be available for patients who are having difficulty and (or) experiencing stress and anxiety related to social interaction.
    • Social skills training leads to better outcomes with reference to symptoms, social functioning, and quality of life, compared with other standard care and (or) other interventions such as supportive psychosocial intervention and occupational therapy. 
  • Life skills training in an evidence-based format should be available for patients who are having difficulty with tasks of everyday living.
    • Life skills training leads to better outcomes with reference to social functioning and quality of life, compared with standard care. 
Cognitive-behavioural interventions
  • Cognitive therapy should be offered to treatment-resistant patients.
    • Randomized controlled studies have shown benefits of CBT for patients with treatment-resistant schizophrenia. 
Family interventions
  • Family interventions should be part of the routine care for patients with schizophrenia.
    • Patients with schizophrenia whose families receive psychoeducation demonstrate reduced rates of hospitalization and show delayed or reduced symptomatic relapse. 
  • Family psychoeducation programs should last more than 9 months and include features of engagement, support, and skills-building, not simply informationor knowledge-sharing.
Peer support, self-help, and recovery
  • Local antistigma campaigns should include contact with people with schizophrenia.
    • Strategies to combat societal stigma and discrimination against the mentally ill are most effective when the public education includes contact with people who have schizophrenia telling their story. 
  • Peer provider services should be included in the continuum of care; such services include consumer roles in group-based skills training, peer support, and public education programs. Peer provider services contribute beneficial role-modelling and experiential knowledge but have not been adequately studied in controlled research designs.
Treatment of comorbid symptoms
  • Cognitive-behavioural interventions should be considered in the treatment of stress, anxiety, and depression in patients with schizophrenia; some adaptation of the techniques used in other populations may be necessary.
    • Symptoms of distress, anxiety, and depression occur in a substantial proportion of patients with schizophrenia. 
    • Psychosocial interventions, particularly cognitive-behavioural interventions used in other populations may be useful in reducing symptoms of stress, anxiety, and depression in patients with schizophrenia. 
Substance use
  • Integrated programs for concurrent substance use disorders should be available for people with schizophrenia
    • The optimal intervention is integrated treatment of both psychosis and substance use in a single program.


Posted in 80 Schizophrenia, 99 Priority Topics, FM 99 priority topics, Psych

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