Pharmacotherapy in Psychotic Disorders

Antipsychotic drugs

• Treat the symptoms of the disorder• Do not cure schizophrenia• Include two major classes:– Dopamine Receptor Antagonists– Serotonin-Dopamine Antagonists

Dopamine Receptor Antagonists

• Effective in the treatment of schizophrenia, particularly the positive symptoms (e.g. delusions).

• Shortcomings:– Only a small percentage of patients are helped enough to

recover a reasonable amount of mental functioning– Associated with both annoying and serious side effects,

including: akathisia and parkinsonianlike symptoms of rigidity and tremor.

• Potential side effects:– Tardive dyskinesia and neuroleptic malignant syndrome

Serotonin-Dopamine Antagonists• Produce minimal or no extrapyramidal symptoms • Interact with different subtypes of dopamine

receptors than do the standard antipsychotics• Affect both serotonin and glutamate receptors. • Produce fewer neurological and endocrinological

adverse effects• Effective in treating negative symptoms of

schizophrenia (e.g. withdrawal) than the typical dopamine receptor antagonist antipsychotic agents.

Approved SDAs

• Risperidone• Clozapine• Olanzapine• Sertindole• Quetiapine• Ziprasidone

Risperidone

• Effective antipsychotic medication• Mild side effects; not associated with

extrapyramidal symptoms• Causes less sedation and fewer anticholinergic

effects than dopamine receptor antagonists• First line agent for first break, mildly to

moderately ill patients and for severely ill, treatment refractory patients

Clozapine• Most effective for severely-ill patients• Risk of significant adverse effects, which are not

found in other SDAs. • Associated with agranulocytosis, requiring weekly

monitoring of neutrophil count. • High risk for seizures and has significant

anticholinergic effects.• Useful for patients refractory to any other

antipsychotic drug and for patients with tardive dyskinesia.

Olanzapine

• Effective medication for treatment of schizophrenia

• Mild profile of adverse effects, different from those of Risperidone.

• Less likely to produce extrapyramidal symptoms

• More likely to produce weight gain, orthostatic hypotension, and constipation.

• Useful first line agent

Sertindole

• Effective agent with transient adverse effects• Must be slowly titrated upward to avoid

orthostatic hypotension• May cause sinus tachycardia, nasal

congestion, and decreased ejaculatory volume• Causes little weight gain and does not cause

anticholnergic symptoms• Ideal for poorly-compliant patients (half life of

3 days).

Quetiapine

• Effective• No increased risk of extrapyramidal symptoms• Main adverse effects include sedation,

tachycardia, weight gain and agitation. • Initial doses must be titrated upward to avoid

orthostatic hypotension and syncope

Ziprasidone

• Effective • Potential additional benefits for patients with

affective symptoms, because it blocks reuptake of serotonin and norepinephrine, and for patients with anxiety because it is an 5-HT1A receptor agonist.

• Adverse effects include sedation, nausea, dizziness, and lightheadedness.

Therapeutic Principles

• Clinicians should carefully define the target symptoms to be treated.

• An antipsychotic that has worked well in the past for a patient should be used again. In the absence of such information, the choice of an antipsychotic is usually based on the adverse effect profile

Therapeutic Principles

• Minimum length of antipsychotic trial us 4 to 6 weeks at adequate dosages. If the trial is unsuccessful, then a different antipsychotic drug, usually from a different class, can be tried.

• In general, the use of more than one antipsychotic medication at a time is rarely, if ever, indicated.

• Patients should be maintained on the lowest possible effective dosage of medication.

Other Drugs

• Combination therapy with one of these drugs and an adjuvant medication may also be tried.

• These are:– Lithium– Anticonvulsants– Benzodiazepines

Lithium• May be effective in reducing symptoms of

psychosis in up to 50% of patients with schizophrenia.

• Usually added with an antipsychotic drug the patient is already taking

• A reasonable drug to try in patients who are unable to take any of the antipsychotic medications.

• Effective in schizophrenia patients with mood swings.

Anticonvulsants

• Carbamazepine or valproate used in combination with lithium or an antipsychotic

• Reduce episodes of violence in some schizophrenia patients

Benzodiazepines

• May exacerbate the severity of psychosis after withdrawal of the drug

• Lorazepam is preferred over diazepam because it is shorter acting and has less abuse potential.

Other Biological Therapies

• Electroconvulsive therapy– Catatonic patients– Patients who cannot for some reason take

antipsychotic drugs

• Psychosurgery– No longer considered an appropriate treatment.– It is however practiced on a limited experimental

basis for severe, intractable cases.

Schizophrenia

A. 2 or more of the ff. symptoms, each present for a significant portion of time during a 1-month period:

1) delusions2) hallucinations3) disorganized speech4) grossly disorganized or catatonic behavior5) negative symptoms (flattened affect,

alogia, avolition)

B. Social/occupational dysfunction- Affects 1 or more major areas of functioning such as work, interpersonal relations, or self care

C. Duration - Continuous signs of the disturbance persist for at least 6 months

D. Schizoaffective and mood disorder exclusion- Rule out by absence of major depressive, manic, or mixed episodes occurring with the active-phase symptoms- If mood episodes have occurred along with active phase symptoms, their total duration should have been brief relative to the duration of the active and residual periods

E. Disturbance is not due to the direct physiological effects of a substance or a general medical condition.

F. Relationship to a pervasive developmental disorder- If with a history of autism or another developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are present for at least a month (or less if successfully treated).

Treatment

• Antipsychotics are mainstay of treatment• 2 main groups:– 1st generation or typical antipsychotics (dopamine

receptor antagonists)– 2nd generation or atypical antipsychotics

(serotonin dopamine antagonists)– Clozapine (Clozaril) – 1st effective antipsychotic

with negligible extrapyramidal side effects

Phases of Treatment

• Acute Phase– Focuses on alleviating the most severe psychotic

symptoms– Lasts between 4-8 weeks– Antipsychotics and benzodiazepines are given

orally or through IM (haloperidol, fluphenazine, olanzapine, ziprasidone, lorazepam)

• Stabilization and Maintenance Phase– Treatment is to prevent psychotic relapse and to

assist patients in improving their level of functioning

– Patients are in a relative state of remission with minimal psychotic symptoms and are placed on maintenance antipsychotics

Typical (1st gen) Antipsychotics

• Phenothiazines– Chlorpromazine– Fluphenazine– Thioridazine

• Thioxantines• Butyrophenones: Haloperidol• Diphenylbutylpiperidines: Pimozide

Atypical (2nd gen) Antipsychotics

• Risperidone• Olanzapine• Quetiapine• Clozapine• Ziprasidone• Less risk for extrapyramidal side effects

• Haloperidol– Drug of choice for acute psychosis if no

contraindications exist – Drawback: High potential for extrapyramidal

symptoms/dystonia

• Quetiapine – Newer antipsychotic used in long term management– Fewer anticholinergic effects– Less dystonia, parkinsonism and tardive dyskinesia

Adverse Effects• Extrapyramidal symptoms and tardive dyskinesia

– most common• Sedation and postural hypotension• Increased prolactin levels• Agranulocytosis – dangerous side effect of

Clozapine• To treat side effects:– Reduce the dose of the drug– Give anti-Parkinson medication– Switch to 2nd generation drugs

Schizophreniform Disorder

A. Criteria A, D, and E of schizophrenia are met.

B. An episode of the disorder (including prodromal, active, and residual phases) lasts at least 1 month but less than 6 months).

Treatment

• Treat psychosis with 3-6 month course of antipsychotics.

• Studies show that schizophreniform patients respond to antipsychotics more rapidly than schizophrenic patients.

• Psychotherapy as adjunctive treatment.• Electroconvulsive therapy – for patients with

marked catatonic or depressed features

Schizoaffective Disorder

A. An uninterrupted period of illness, during which, at some time, there is either a major depressive episode, a manic episode, or a mixed episode concurrent with symptoms that meet Criterion A of schizophrenia.

B. During the same period of illness, there have been delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms.

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

D. Disturbance is not due to the direct physiological effects of a substance or a general medical condition.

Treatment

• Mainstay of treatment are mood stabilizers and antipsychotics.

• Carbamazepine found to be superior to lithium in patients with major depressive disorder.

• If patient is in maintenance phase, decrease dosage of drug to avoid adverse effects on other organ systems.

• Antidepressants can also be given– SSRIs (fluoxetine) and sertraline are first-line

agents because they have less effect on cardiac status and have a favorable overdose profile.

• For manic or agitated patients– May benefit from a tricyclic drug– Electroconvulsive therapy should be considered

Delusional Disorder

A. Nonbizarre delusions (ex. Involves situations that occur in real life, such as being stalked, poisoned, diseased, or being deceived by a lover, etc.) of at least 1 month duration.

B. Does not meet Criterion A for schizophrenia.C. Apart from the impact of the delusion/s or its

ramifications, functioning is not markedly impaired and behavior is not obviously odd or bizarre.

D. If mood episodes have occurred concurrently with delusions, their total duration has been brief relative to the duration of the delusional episodes.

E. Disturbance is not due to the direct physiological effects of a substance or a general medical condition.

Treatment

• Intervention is focused more on managing the morbidity of the disorder by reducing the impact of the delusion on the patient’s (and family’s life).

• One-on-one psychotherapy sessions.• Antipsychotic drugs are still mainstay of

treatment.• Give antidepressants if patient has features of

a mood disorder.

Brief Psychotic Disorder

A. Presence of 1 (or more) of the ff. symptoms1) delusions2) hallucinations3) disorganized speech4) grossly disorganized or catatonic behavior

B. Duration of an episode of the disturbance is at least 1 day but less than 1 month, with eventual full return to premorbid level of functioning.

C. Disturbance is not better accounted for by a mood disorder with psychotic features, schizoaffective disorder, or schizophrenia and is not due to the direct physiologic effects of a substance or general medical condition.

Treatment

• Antipsychotics and benzodiazepines are mainstay treatment.

• Anxiolytic medications can be given during the first 2-3 weeks after resolution of the psychotic episode.

Other Psychotic Disorders

• Psychotic Disorder Not Otherwise Specified• Nonorganic Psychotic Disorders• Postpartum Psychosis• Shared Psychotic Disorder (Folie a Deux)• Psychotic Disorder due to a General Medical

Condition• Substance-Induced Psychotic Disorder