Schizophreniform Disorder Medication
- Author: Ravinder N Bhalla, MD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK) more...
Several medications are used to treat schizophreniform disorder. Agent selection depends on whether the depressive or the manic subtype is present. Early treatment with medication, along with good premorbid function, often improves outcomes.
In the depressive subtype, combinations of antidepressants (eg, sertraline, fluoxetine) plus an antipsychotic (eg, haloperidol, risperidone, olanzapine, aripiprazole, or ziprasidone) are used. In refractory cases, clozapine has been used as an antipsychotic agent. In the manic subtype, combinations of mood stabilizers (eg, lithium, carbamazepine, and valproic acid) plus an antipsychotic are used.
Antipsychotic agents ameliorate psychosis and aggressive behavior.
Haloperidol is used for managing psychosis, as well as motor and vocal tics in children and adults. The mechanism of action is not clearly established, but the drug exerts a selective effect on the central nervous system (CNS) by competitively blocking postsynaptic dopamine D2 receptors in the mesolimbic dopaminergic system; increases in dopamine turnover are responsible for the tranquilizing effect. With subchronic therapy, depolarization blockade and D2 postsynaptic blockade are responsible for antipsychotic action.
Risperidone is a selective monoaminergic antagonist that binds to dopamine D2 receptors with a 20 times lower affinity than it binds to serotonin type 2 (5-HT2) receptors. It also binds to alpha1-adrenergic receptors, with lower affinity to H1-histaminergic and alpha2-adrenergic receptors. It improves negative symptoms of psychosis and decreases occurrence of extrapyramidal effects. Risperidone is also available in a long-acting intramuscular (IM) formulation.
Olanzapine is an atypical antipsychotic with a broad pharmacologic profile across receptor systems (eg, serotonin, dopamine, cholinergic muscarinic, alpha-adrenergic, and histamine). Its antipsychotic effect is exerted through antagonism of dopamine and serotonin type 2 receptors. Olanzapine is indicated for treatment of psychosis and bipolar disorder.
Clozapine (Clozaril, FazaClo)
Clozapine has a weak affinity for D1, D2, D3, and D5 receptors and a high affinity for D4 receptors. It also acts as an antagonist at adrenergic, cholinergic, histaminergic, and serotonergic receptors. However, clozapine does not induce catalepsy, nor does it inhibit apomorphine-induced stereotypy. The risk of agranulocytosis limits the use of this agent to patients who are nonresponsive to or intolerant of classic neuroleptic agents.
Quetiapine is a newer antipsychotic used for long-term management. It may antagonize dopamine and serotonin effects. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.
Ziprasidone antagonizes D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, and alpha1-adrenergic receptors. It has a moderate antagonistic effect for histamine H1. It moderately inhibits reuptake of serotonin and norepinephrine.
Aripiprazole improves positive and negative schizophrenic symptoms. Its mechanism of action is unknown but is hypothesized to differ from that of other antipsychotics. Aripiprazole shows high affinity for D2, D3, 5-HT1A, and 5HT2A receptors; shows moderate affinity for D4, 5HT2C, 5-HT7, alpha1 adrenergic, and H2 receptors; and possesses moderate affinity for the serotonin reuptake transporter. It is thought to be a partial D2 and 5-HT1A agonist and a 5-HT2A antagonist. No QTc-interval prolongation is noted in clinical trials.
Iloperidone is an atypical antipsychotic agent that is indicated for acute treatment of schizophrenia. Its precise mechanism of action is unknown. It antagonizes D2 and 5-HT2 receptors. However, it shows high affinity for 5-HT2A, D2, and D3 receptors and low-to-moderate affinity for D1, D4, H1, 5-HT1A, 5HT6, 5-HT7, and NE alpha1 receptors.
Paliperidone is the active metabolite of risperidone. Its therapeutic effects consist of mixed central serotonergic and dopaminergic antagonism. Unlike risperidone, paliperidone exhibits 10-fold lower affinity for alpha-2 and 5-HT2A receptors and almost 3- to 5-fold lower affinity for 5-HT1A and 5HT1D, respectively.
Lurasidone is an atypical antipsychotic, and its precise mechanism of action is unknown. Its suggested efficacy is thought to be due to mediation of central D2 and 5HT-2A receptor antagonism. It is a partial agonist for 5-HT1A receptors with high affinity for D2, 5-HT2A, and 5HT7 receptors and moderate affinity for alph-2C-adrenergic receptors.
The mechanism of action of asenapine maleate is unknown. Its efficacy is thought to be mediated via combined antagonist activity at D2 and 5-HT2 receptors. The addition of serotonin antagonism to dopamine antagonism may improve the negative symptoms of psychoses and may reduce the incidence of extrapyramidal adverse effects when compared with typical antipsychotics. It is indicated for acute treatment and maintenance therapy of schizophrenia.
Clinical experiences have shown that patients with bipolar disorder have fewer episodes of mania and depression when treated with mood-stabilizing drugs. These medications serve to stabilize the patient’s mood, as the name implies. They also can dampen extremes of mania or depression.
Lithium is the drug commonly used for prophylaxis and treatment of manic episodes. A recent study suggests that lithium may also have a neuroprotective role.
Lithium is indicated to treat bipolar disorder. The specific mechanism of action is unknown, but the drug alters sodium transport in nerve and muscle cells and influences reuptake of serotonin, norepinephrine, or both at cell membranes.
Antidepressants decrease aggression and treat the underlying illness. Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred to the other antidepressant classes. Because the adverse-effect profiles of SSRIs are less prominent than those of other drugs, improved compliance is promoted. SSRIs do not have the cardiac dysrhythmia risk associated with tricyclic antidepressants (TCAs). Dysrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered in treating a child or adolescent with a mood disorder.
Physicians are advised to be aware of the following information and to use appropriate caution when they consider treatment with SSRIs in the pediatric population.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory stating that most SSRIs are not suitable for use by persons younger than 18 years for treatment of depressive illness. After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except in the case of fluoxetine, which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality in clinical trials of various antidepressant drugs in pediatric patients. The FDA asked that additional studies be performed because suicidality occurred in both treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Fluoxetine is an SSRI used to treat impulse-control problems or underlying illness. It selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine.
Sertraline is an SSRI used to treat impulse-control problems or underlying illness. It selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine.
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance, the dosing should be adjusted so as to maintain the patient on the lowest effective dosage, and the patient should be periodically reassessed to determine the need for continued treatment.
Fluvoxamine enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than TCAs do. Fluvoxamine has been shown to reduce repetitive thoughts, maladaptive behaviors, and aggression and to increase social relatedness and language use.
Citalopram enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. No head-to-head comparisons of SSRIs have been done; however, on the basis of metabolism and adverse effects, citalopram is considered the SSRI of choice for patients with head injury.
Escitalopram is an SSRI and an S-enantiomer of citalopram. It is used for the treatment of depression. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS, resulting from inhibition of CNS neuronal reuptake of serotonin. The onset of depression relief may be obtained after 1-2 weeks—sooner than is possible with other antidepressants.
Some anticonvulsants work as mood stabilizers to correct the mood imbalance associated with bipolar disorder.
Valproic acid may increase brain gamma-aminobutyric acid (GABA) levels by inhibiting aminobutyrate aminotransferase. GABA inhibits presynaptic and postsynaptic discharges. In addition to its use as a mood stabilizer, valproic acid is also used for migraine headaches, epilepsy, and mania.
Oxcarbazepine's pharmacologic activity is primarily from its 10-monohydroxy metabolite (MHD). It may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Its anticonvulsant effect may also be achieved by affecting potassium conductance and high-voltage activated calcium channels.
Drug pharmacokinetics are similar in children older than 8 years and in adults. Children younger than 8 years have a 30-40% increased clearance as compared with older children and adults. Use of oxcarbazepine in children younger than 2 years has not been studied in controlled trials.
Carbamazepine is indicated for treatment of epilepsy and trigeminal neuralgia. Research and clinical experience indicate that it is effective in treating manic subtype schizoaffective disorder.
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