schizophrenia
SCHIZOPHRENIA
Schizophrenia is a devastating mental illness characterized by symptoms eg hallucinations, disorganized thinking, loss of goal-directed behaviors and deterioration in social role functioning.
Positive or psychotic symptoms are delusions, hallucinations, and distorted perceptions.
Negative symptoms include flat or blunted emotions, lack of motivation or energy, lack of pleasure or interest in things, and limited speech.
Disorganized symptoms are confused thinking, disorganized speech and behavior.
Cognitive symptoms include impairment in attention verbal fluency memory, and executive functioning.

Principles of Therapy

General Treatment Principles

  • Choice of agent will be based on STEPS principle which means Safety, Tolerability, Efficacy, Price, Simplicity:
    • Will also consider side effects profile, prior response history of patient or family member, patient preference and intended route of administration
  • Maximize benefits of pharmacological therapy and minimize side effects
  • Monotherapy is preferred and polypharmacy should be avoided
  • Antipsychotics remain the primary treatment for schizophrenia
    • Use with caution in the elderly because of increased risk of mortality from sudden cardiac death and cardiovascular accidents
    • Older, first-generation antipsychotics are generally considered to have minimal risk of teratogenicity

Pharmacotherapy

Atypical Antipsychotics

  • Atypical antipsychotics are now generally preferred over the conventional antipsychotics
  • Effects: Have been found to be equivalent or superior to conventional antipsychotics for the treatment of psychotic symptoms and thought disorganization
    • Some may have superior effect on negative symptoms than conventional antipsychotic drugs
    • Most atypical antipsychotics have similar likelihood of causing extrapyramidal symptoms (EPS) as in conventional antipsychotics with lower-potency dopamine D2 neuroreceptor blockade (eg Chlorpromazine, Thioridazine, Perphenazine)
  • All patients are recommended to have regular monitoring of weight, body mass index (BMI), serum lipids and fasting glucose levels
    • Atypical antipsychotics have been shown to cause weight gain and metabolic side effects

Amisulpride

  • Appears to have benefits against negative symptoms at lower doses and at higher doses tends to be more effective against positive symptoms
  • Has favorable side effects profile, but can cause hyperprolactinemia and higher doses increase risk for extrapyramidal symptoms occurrence

Aripiprazole

  • Appears to be as effective as Haloperidol in the treatment of schizophrenia
    • May also be used for treatment of acute aggression in schizophrenia
  • Extrapyramidal symptoms-related adverse effects have been shown to be comparable to placebo
  • May have a higher risk of insomnia compared to conventional antipsychotics, but less risk of raised prolactin and prolongation of the QTc interval than other atypicals

 

Clozapine

  • Has been shown to be useful in patients who do not respond to conventional antipsychotics
    • Superior to conventional antipsychotics in terms of symptom reduction and risk of relapse
  • Drug of choice in the treatment of chronic and severe aggression in schizophrenia
    • Studies have shown that patients maintained on Clozapine had fewer aggressive episodes and less suicide attempts compared with other antipsychotics
    • Should be considered if there is significant and continuously increased risk of suicide
  • In patients who were diagnosed to have both schizophrenia and alcohol use disorder, Clozapine seems to be effective in reducing craving and substance intake
  • Avoid use in patients with history of seizure as it may lower seizure threshold
  • Licensed for use only in treatment of refractory schizophrenia due to life-threatening side effect
    • Clozapine causes agranulocytosis in approximately 1% of patients
    • Regular and careful monitoring of white blood cell (WBC) count is necessary

Olanzapine

  • At least as effective as conventional antipsychotics
    • May also be used for treatment of acute or chronic aggression in schizophrenia
  • Generally well tolerated and does not tend to cause extrapyramidal symptoms at therapeutic doses
    • Major side effects are weight gain, hyperlipidemia as part of metabolic syndrome and hyperglycemia

Paliperidone

  • Indicated for acute and maintenance treatment of schizophrenia in adults and adolescents (12-17 years of age) and adults with schizoaffective disorder
  • It is not extensively metabolized in the liver
  • Compared with other atypical antipsychotics, studies showed similar efficacy and lower odds of weight gain and undesirable metabolic side effects
  • Major active metabolite of Risperidone

Quetiapine

  • At least as effective as conventional antipsychotics in the treatment of schizophrenia
  • Very rarely causes extrapyramidal symptoms at any dose
    • Orthostatic hypotension may occur during the initial titration period and at high doses

Risperidone

  • At least as effective as conventional antipsychotics
    • May also be used for treatment of acute aggression in schizophrenia
  • When used at recommended doses (<6 mg/day), it has very low rate of extrapyramidal symptoms
    • Higher doses increase risk of extrapyramidal symptoms
    • Hyperprolactinemia and postural hypotension may also occur

Ziprasidone

  • At least as effective as conventional antipsychotics
    • May also be used for treatment of acute aggression in schizophrenia
    • Has been shown to have beneficial effects on symptoms of depression
  • Has been associated with prolongation of the QTc interval; dose needs to be adjusted based on therapeutic and side effects

Conventional Antipsychotics

  • Eg Haloperidol, Perphenazine, Molindone
  • All antipsychotics in this class vary in potency and overall side effects profile, but have similar overall efficacy
  • Effects: Patients demonstrate a decrease in positive symptoms, thought disorder, blunted effect, withdrawal retardation and autistic behavior
    • 60% of patients treated for 6 weeks with conventional antipsychotics achieve complete remission or experience only mild symptoms
    • All conventional antipsychotics can cause a broad range of side effects due to their effects on receptors other than the target therapeutic site including extrapyramidal symptoms and tardive dyskinesia

Haloperidol

  • Has been shown to be useful in the management of acute aggression in schizophrenia
    • Most commonly used conventional antipsychotic in the emergency room setting
    • May be first-line agent in acute aggression especially if affordability is an issue
    • Cheaper compared with atypical antipsychotics
  • Benzodiazepine may also be administered with Haloperidol to enhance the sedative effect

Molindone

  • Studies have suggested that Molindone may be equally effective as atypical agents
    • A clinical trial, comparing Molindone with Risperidone and Olanzapine in pediatric patients with early-onset schizophrenia and schizoaffective disorder, showed no significant difference in terms of reduction of symptom severity

Perphenazine

  • Studies have suggested that Perphenazine may be equally effective as atypical agents
    • A clinical trial, comparing Perphenazine with Risperidone, Olanzapine, Quetiapine and Ziprasidone in adult patients, showed Olanzapine was most effective in terms of rates of discontinuation, but overall efficacy was similar among the drugs; extrapyramidal symptoms were uncommon and metabolic side effects were most seen in Olanzapine use
  • For some patients, conventional agents such as Perphenazine may be an appropriate first-line treatment

Route of Administration

Oral

  • Typically used for acute and maintenance treatment
  • Reaches peak concentration in 2-3 hours which gives a calming effect
    • May take several days-weeks to see the true antipsychotic effects

Short-Acting Intramuscular (IM)

  • Quick onset of action is an advantage when calming effects are needed to treat agitation
  • Peak concentration is reached in 30-60 minutes after administration

Depot Formulations

  • Recommended for patients who have trouble taking oral medications reliably, who deny illness or who have poor insight or for those who prefer depot
  • Limited number of conventional and atypical antipsychotics are available in this form
  • Require 3-6 months to reach steady-state therefore seldom used alone during acute treatment when the dose needs to be adjusted based on therapeutic and side effects

Non-Pharmacological Therapy

Acute Phase Treatment

Treatment Settings

  • Outpatient vs inpatient treatment will depend on assessment of patient’s safety, safety of others and the patient’s level of functioning
  • Inpatient treatment is indicated if the patient has a serious threat of harm to self or others, unable to care for self or needs constant supervision

Psychiatric Management

  • Goals: Prevent harm, control disturbed behavior, suppress symptoms and return to the best level of functioning
  • Build a therapeutic alliance with the patient and the patient’s family
  • Educate the patient (to the best of their level of understanding) and the patient’s family/caregiver about the illness
  • Establish short- and long-term treatment plans

Psychosocial Interventions

  • Goals: Reduce overstimulating or stressful environments, relationships or life events
  • Promote reduced disease arousal by giving simple, clear communications and expectations
  • Help provide a structured and predictable environment which includes low performance requirements
  • Help to establish non-demanding, supportive relationships between the patients and their treatment team

Stabilization Phase

Psychiatric Management

  • Goals: Minimize stress on the patient and provide support to minimize chances of relapse
  • Assist in the patient’s adaptation to life in the community
  • Help in maintaining the continued reduction of symptoms and consolidation of remissions
  • Continue to educate the patient about the course and outcome of the illness
  • Promote adherence to treatment regimen by educating the patient and their families about the chances of relapse with discontinuation of medication

Psychosocial Interventions

  • Psychoeducation to promote compliance
  • Start on social and community interventions
    • Therapeutic community interventions
    • Rehabilitation eg social skills training, vocational training, cognitive-behavioral therapy (CBT), cognitive remediation therapy (CRT)
    • Self-help groups formed by patients, self-treatment organizations and relative organizations (formed mostly by patient’s parents)
  • Individual therapy
    • Supportive and insight-oriented
    • Individualized approach based on clinical condition, coping capabilities and preferences
  • Family interventions
    • Involve the family in treatment planning, goal setting and service delivery
    • Provide education, support, guidance and training to assist family members fulfill their role as caregivers
    • Support groups for families should be suggested
  • Group therapy
    • Group psychotherapy and support groups help enhance problem solving, goal planning, social interactions and medication side effects
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