Transcript Pharmacotherapy in Psychotic Disorders

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
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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) delusions
2) hallucinations
3) disorganized speech
4) grossly disorganized or catatonic
behavior
5) 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
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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. symptoms
1) delusions
2) hallucinations
3) disorganized speech
4) 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
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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