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Schizophrenia

Topics / Psychiatry / Schizophrenia Spectrum Disorders

Basics

The prevalence is around 1%. Used to be called “Dementia Praecox” by Emil Kraepelin, then named “Schizophrenia” in 1908 by Eugen Bleuler. It is a chronic dopamine disorder. Therefore, most of the antipsychotics’ efficacy is linked to their ability to block the D2 receptor. However, other hypotheses are also available (Glutamate disorder, Serotonin disorder, GABA disorder). Earlier age of onset for males (early-mind 20s) vs females (late 20s). Rarely presents before age 15 or after age 55. Suicide risk is high: 5% die by suicide, 20% will attempt suicide and many will have suicidal ideation. Patients have a high genetic predisposition. The patients also have a high comorbid use of substances (Nicotine > Alcohol > Cannabis > Cocaine)

Pathophysiology

The four dopamine pathways
 
  1. Mesolimbic Pathway: Known as the reward pathway. It connects the ventral tegmental area (VTA in the midbrain) to the ventral striatum (prefrontal cortex), which includes the Nucleus accumbens (NA). In Schizophrenia there is an increased level of Dopamine in this tract which results in positive symptoms.
  2. Mesocortical Pathway: It connects the ventral tegmental area to the (prefrontal cortex). In Schizophrenia, there is decreased levels of Dopamine in this tract resulting in negative and cognitive symptoms.
  3. Nigrostriatal Pathway: It connects the zona compacta of the substantia nigra to the caudate and putamen nuclei of the striatum. The anti-psychotics block this pathway. Therefore, it results in extra-pyramidal side effects and tardive dyskinesia.
  4. Tuberohypophyseal Pathway: It connects the arcuate nucleus (hypothalamus) to the pituitary gland. The anti-psychotics block this pathway. Therefore, it results in hyperprolactinemia as a side effect.

Phases

Schizophrenia has 3 phases: The Prodromal, Psychotic, and Residual phases. The prodromal phase can be characterized by negative symptoms and it precedes the psychotic phase. The patient becomes socially withdrawn and may have some decline in overall function. In the Psychotic phase, the patient begins to manifest more positive symptoms. Finally, in the residual phase, the patient will have milder symptoms of the psychotic phase.

Prognostic Factors

  1. Better Prognosis: Later onset, has positive symptoms, mood symptoms, acute onset, female gender, fewer relapses, has good social support, and had a good level of function before.
  2. Worse Prognosis: The opposite of the above.

Presentation

  1. Positive Symptoms: Delusions, Hallucinations, Disorganized speech, Disorganized behavior
    1. These symptom respond to anti-psychotics
  2. Negative Symptoms: Alogia (poverty of speech), affect flattening, Attention is poor, Avolition (loss of motivation), anhedonia (lack of pleasure), Asociality (lack of motivation to engage in social interactions)
    • These symptoms do not respond well to anti-psychotics. They also causes the patient to become more socially isolated and impairs the patient’s function.
    • They also mimic a mood disorder ( depression )
  3. Cognitive Symptoms: These symptoms include impairment in working memory, executive function and attention.

Diagnostic Criteria

We use the DSM-V, which came out in 2013. Some doctors still use the DSM-IV, which came back out in 1994.

Diagnostic Criteria (DSM-V)
A Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be (1 ), (2), or (3):
  1. Delusions
  2. Hallucinations
  3. Disorganized speech (e.g., frequent derailment or incoherence)
  4. Grossly disorganized or catatonic behavior
  5. Negative symptoms (i.e., diminished emotional expression or avolition)
B Functional deterioration: Level of function in one or more major areas (occupation, social, self-care) is markedly below prior to the onset
C Continuous disturbance persists for at least 6 months. This includes the prodromal or residual phases!
D You ruled out other psychotic or mood disorders
E You ruled out effects of substances or another medical condition (AMC)
Some of these patients may develop catatonia.
  1. Mood Disorder (Major Depressive or Bipolar Disorder) with psychotic or catatonic features
  2. Schizoaffective disorder – Needs a mood episode (depressive or manic episode) with the symptoms of Schizophrenia and they must be present for the total duration of the active periods.
  3. Brief psychotic disorder (Symptoms of Schizophrenia present but for more than 1 day but less than 1 month)
  4. Schizophreniform disorder (Symptoms of Schizophrenia present but for more than 1 month and less than 6 months)
  5. Delusional Disorder: Does not meet the criteria for Schizophrenia.
  6. Substance induced Psychotic Disorder
  7. Psychotic disorder due to AMC.

Investigations

  1. Baseline psychiatry bloods
  2. Rule out medical conditions
  3. Rule out substance use that may have a psychotic effect: Ask thorough history, perform substance-specific tests (blood, urine).
  4. Read work up for Delirium/Acute Confusional State

Treatment

1. Non-Pharmacological

  1. Once the diagnosis is confirmed, treatment should be done in consultation with a Psychiatrist.
  2. Psychoeducation should be provided to the patient, family or caretaker.
  3. Other modalities: Behavioral therapy, Family therapy, Group therapy.
  4. If in reproductive age: Advice family planning, the patient is a parent already then one should consider referral to a social worker for possible grants. All antipsychotics, except Clozapine, are considered safe in pregnancy.
  5. Monitor compliance and perform adherence counseling if necessary.
  6. Provide education on lifestyle modification
  7. Screen and manage any substance use disorder
  8. Screen and treat any comorbidities: Hypertension, Diabetes Mellitus
  9. Monitor side effects: Extrapyramidal side effects, for instance, BMI and blood glucose every 6 months. However, other side effects should be asked about at every visit.
  10. Social worker may be needed for “placement” of the patient into a specialized facility.

2. Pharmacological

  1. Manage the aggressive patient if necessary.
  2. Initiation of Treatment:
    • Haloperidol started as 0.75 – 1.5mg PO daily, increasing to 5mg PO daily.
      1. If the patient is then having a good response to Haloperidol or is able to tolerate Haloperidol, one may consider a depot antipsychotic.
      2. Flupenthixol decanoate 10-40mg every 4 weeks OR Zuclopenthixol decanoate 200-400mg every 4 weeks.
    • If the patient has a poor response OR they tolerate Haloperidol poorly OR they are at a high risk of Tardive Dyskinesia OR they are at a high risk of EPSE:
      1. Start on Risperidone (Instead of Haloperidol) 2 – 4mg PO nocte, with a maximum dose of 6mg PO nocte OR
      2. Chlorpromazine 75 – 300mg PO daily in divided doses.
    • If the patient has a poor response OR they tolerate the medications (Haloperidol/Risperidone/Chlorpromazine) poorly then:
      1. Start on Olanzapine 5mg PO nocte, increased to 10mg PO nocte. The maximum dose should be 20mg PO nocte and this medication should be specialist initiated.
    • Lastly, if the patient has a poor response or meets the criteria for initiation of Clozapine then this agent should be used. However, this should be done by a specialist AND as an inpatient)

Notes

  1. Before Neuroleptics: Sleep therapy, shock therapy and insulin coma therapy, lobotomies -Horrible stuff!
  2. First generation vs second generation antipsychotics.
    1. Efficacy is mostly the same. These drugs do not have much effect on the cognitive disability of Schizophrenia. The treatment should be taken for at least 4 weeks before one can determine the efficacy.
    2. First generation:
      1. Drugs: Chlorpromazine, Fluphenazine, Haloperidol
      2. Mostly D2 Antagonists, able to treat the positive symptoms but not much effect on the negative symptoms
  • More extra-pyramidal side effects (EPSE), neuroleptic malignant syndrome, and tardive dyskinesia
  1. Second generation:
    1. Drugs: Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprasidone
    2. Mostly, D4 > D2 antagonist, as well as other receptors such as antagonizes the serotonin receptors. They have a lower incidence of EPSE but have more risk of metabolic syndrome. Clozapine should only be used once when indicated since these patients may have agranulocytosis as a side effect.
  2. Another article will be written to discuss antipsychotics and their side effects.
Published on August 30, 2022
Dr RW Becerra Estevez
Dr RW Becerra EstevezMBChB (WSU)

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