Schizophreniform Disorder 

Updated: Dec 11, 2018
Author: Ravinder N Bhalla, MD; Chief Editor: David Bienenfeld, MD 

Overview

Practice Essentials

Schizophreniform disorder is characterized by the presence of the symptoms of schizophrenia, but it is distinguished from that condition by its shorter duration, which is at least 1 month but less than 6 months.

Signs and symptoms

A detailed history should be obtained, focusing on the following:

  • Time of symptom onset

  • Course

  • Premorbid functioning

  • Precipitants

  • Physical health

  • Use of medications

  • Use of alcohol and other substances

  • Family history

  • Previous episodes (if any)

It is important to distinguishing schizophreniform disorder from other medical and psychiatric conditions that may present in a floridly psychotic state.

The following are generally indicated:

  • Toxicologic evaluation

  • Medical evaluation

  • Full Mental Status Examination

See Presentation for more detail.

Diagnosis

Alternative diagnoses to be considered include the following:

  • Schizophrenia

  • Brief psychotic disorder

  • Substance- or medication-induced psychotic disorder

  • Bipolar affective disorder

  • Depression

  • Delirium

  • Schizoaffective disorder

  • Psychotic disorder due to another disease or its treatment

  • Delusional disorder

  • Schizotypal, schizoid, or paranoid personality disorder

  • Autism spectrum disorder

  • Disorders presenting in childhood with disorganized speech

  • Attention deficit hyperactivity disorder

  • Obsessive-compulsive disorder

  • Posttraumatic stress disorder

  • Traumatic brain injury

For schizophreniform disorder, as for schizophrenia, there are currently no specific laboratory or psychometric tests.

See DDx and Workup for more detail.

Management

The general aims of treatment are as follows:

  • To protect and stabilize the patient

  • To minimize the psychosocial consequences

  • To resolve the target symptoms with minimal adverse effects

General treatment approaches are as follows:

  • Psychotherapy

  • Family and social-educational therapies

  • Pharmacotherapy

Pharmacotherapy for schizophreniform disorder is similar to that for schizophrenia. Medications used include the following:

  • Risperidone

  • Olanzapine

  • Quetiapine

  • Ziprasidone

  • Aripiprazole

  • Paliperidone (major active metabolite of risperidone)

  • Asenapine

  • Iloperidone

  • Lurasidone

Ziprasidone and aripiprazole are also available in injectable forms, which are less likely to cause acute extrapyramidal side effects.

Electroconvulsive therapy (ECT) is generally reserved for medication-resistant cases of schizophreniform disorder.

See Treatment and Medication for more detail.

Background

Schizophreniform disorder is a serious mental disorder with symptoms similar to those of schizophrenia. Early diagnosis of this disorder is crucial, as is early intervention with medication, supportive therapy, and patient and family education.

According to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),[1] schizophreniform disorder is characterized by the presence of the symptoms of schizophrenia, including delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, and negative symptoms. The disorder, including its prodromal, active, and residual phases, lasts longer than 1 month but less than 6 months.

Unlike schizophrenia, in which prodromal symptoms may develop over several years, schizophreniform disorder requires, among other features, a rather rapid period from the onset of prodromal symptoms to the point at which all criteria for schizophrenia (except duration and deterioration) are met (≤6 months).

Diagnostic criteria (DSM-5)

The specific DSM-5 criteria for schizophreniform disorder are as follows[1] :

  • The presence of 2 (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated), with at least 1 of them being (1), (2), or (3): (1) delusions, (2) hallucinations, (3) disorganized speech, (4) grossly disorganized or catatonic behavior, and (5) negative symptoms

  • An episode of the disorder lasts at least 1 month but less than 6 months; when the diagnosis must be made without waiting for recovery, it should be qualified as “provisional”

  • Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms or (2) any mood episodes that have occurred during active-phase symptoms have been present for a minority of the total duration of the active and residual periods of the illness

  • The disturbance is not attributable to the physiologic effects of a substance (eg, a drug of abuse or a medication) or another medical condition[2]

Schizophreniform disorder is further specified as being either with or without good prognostic features.[1] The specifier “with good prognostic features” requires the presence of at least 2 of the following:

  • Onset of prominent psychotic symptoms within 4 weeks of the first noticeable change in usual behavior of functioning

  • Confusion or perplexity

  • Good premorbid social or occupational functioning

  • Absence of blunted or flat effect

In the absence of 2 or more of these 4 features, the specifier “without good prognostic features” is employed.

Pathophysiology

Patients with schizophreniform disorder and patients with schizophrenia share many anatomic and functional cortical deficits on neuropsychological studies, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET).

A study of delay-dependent memory performed by Mathes et al found that patients with schizophreniform disorder and schizophrenia were less able to form an internal representation of complex objects.[3] Such neuropsychological tests help clinicians further understand the psychopathology of the disorder.

The study by Mathes et al investigated 55 patients with schizophreniform psychosis, 50 patients with established schizophrenia, and a control group of 56 healthy controls, using the delayed matching-to-sample task from the Cambridge Neuropsychological Test Automated Battery (CANTAB).[3] Performance deficits were found in both patient groups after age and premorbid intelligence quotient (IQ) were controlled for.

Even when simultaneous matching-to-sample ability (ie, perceptual matching) was controlled for, impaired performance in both patient groups was found as soon as the stimuli were removed.[3] Impaired performance was not due to different types of performance errors in patients as compared with control individuals. Performance in the 2 patient groups was comparable, except for a slight decrease in overall task performance. These findings suggest that the deficit is relatively stable during the course of the illness.

The similarity of the deficits notwithstanding, schizophreniform disorder is distinct from schizophrenia. This distinction was confirmed by a trial by Sautter et al, which compared the courses of illness (including positive and negative symptoms of psychosis, interpersonal and occupational role functioning, and other aspects of the deficit) in 36 patients who received a diagnosis of either schizophreniform disorder or schizophrenia.[4]

Approximately 3.5 and 4 years after their initial index hospitalization, the 2 groups of patients were compared.[4] In the patients with schizophreniform disorder, the level of negative symptoms was low at both follow-up examinations. In the patients with schizophrenia, however, the level of negative symptoms was higher at first but fell significantly over time. The findings of this trial indicate that the course of schizophreniform disorder differs from that of schizophrenia.

Epidemiology and Prognosis

The prevalence of schizophreniform disorder, like that of schizophrenia, is equally distributed between the sexes, with peak onset between the ages of 18 and 24 years in men and between the ages of 24 and 35 years in women.

The persistence of symptoms beyond 6 months predicts a worse prognosis for schizophrenia as compared with schizophreniform disorder. Clarke et al demonstrated that a longer period of untreated psychosis was linked with a significantly worse functional and symptomatic outcome at 4 years’ follow-up.[5]

Confusion and perplexity at the height of the psychotic episode correlates with better outcome in schizophreniform disorder. A significant risk of suicide exists in patients with this disorder, especially when they are more likely to go into a depression after the psychotic period.[6] Psychotherapy during this phase, aimed at helping patients understand the psychotic episodes, is likely to improve the prognosis and enhance recovery. Drake et al found that patients who acquired better insight into their illness were less likely to experience relapse.[7]

Fraguas et al examined the diagnostic stability and the functional outcome of patients with early-onset psychosis, including schizophreniform disorder, over a 2-year follow-up period; they found a 50% predictability for future psychotic episodes for schizophreniform disorder and cited the presence of negative symptoms as a predictor of lower level of functioning at the end of 2 years.[8]

According to the American Psychiatric Association, approximately two thirds of patients diagnosed with schizophreniform disorder progress to a diagnosis of schizophrenia. According to Benazzi et al, patients with a good prognosis tend to be retrospectively associated with the affective spectrum of diagnoses rather than the schizophrenic.[9]

According to Troisi et al, in some patients with a schizophreniform disorder, the presence of negative symptoms and poor eye contact appear to be prognostic of a poor outcome.[10] Studies have not yet elicited a consensus about whether ventricular enlargement is predictive of poor outcome in patients with a schizophreniform disorder.

Patient Education

Efforts should be made to educate both patients and their families about the early signs of relapse and the need for continuing treatment. Such efforts advance the overall aim of helping patients regain productive roles in society while reducing the risk of relapse. Families with a high degree of emotional expression are likely to cause additional stress to the patient and to increase the likelihood of relapse.

The patient’s condition, the patient’s family, and the patient’s system of care are a few of the many factors that likely affect treatment engagement early in the course of schizophreniform disorder and schizophrenia. Clinicians should give special attention to these factors when caring for patients who experience their first episode of schizophreniform disorder.

The following links provide valuable information for patients and their families:

  • Schizophrenia - National Institute of Mental Health (NIMH)

  • American Psychiatric Association

  • Schizophrenia Research Forum

For patient education resources, see the Mental Health and Behavior Center, as well as Schizophrenia.

 

Presentation

History

A detailed history (which may require the assistance of family members or others familiar with the patient) should be obtained, focusing on the following:

  • Time of symptom onset

  • Course

  • Premorbid functioning

  • Precipitants

  • Physical health

  • Use of medications

  • Use of alcohol and other substances

  • Family history

  • Previous episodes (if any)

Distinguishing schizophreniform disorder from other medical and psychiatric conditions that may present in a floridly psychotic state can be challenging.[11] Such conditions include schizophrenia; brief psychotic disorder; substance-induced mood disorders, depression, and mania; bipolar affective disorder; and depression (see DDx).

The symptom profile of a schizophreniform disorder is identical to that of schizophrenia; however, the total duration of illness, including prodromal or residual phases, must be less than 6 months. Also, a deterioration in social or occupational functioning, which is required to make the diagnosis of schizophrenia, is not required for schizophreniform disorder.

A diagnosis of brief psychotic disorder requires that symptoms last at least 1 day but no longer than 1 month. A diagnosis of schizophreniform disorder, like a diagnosis of schizophrenia, requires that symptoms be present for at least 1 month.

Although substance-induced psychoses frequently resolve in less than 1 month, sustained substance-induced psychoses in abstinent persons may be indistinguishable from schizophreniform disorder. In the absence of objective diagnostic criteria, the distinction is made on the basis of the extent to which the clinician believes substances have contributed to the current symptom profile.

In bipolar disorder and major depression with mood-incongruent features, the affective symptoms are clearly more prominent. In mood disorder, the psychotic symptoms are secondary and less intense if present. Sometimes, in the absence of an accurate history, diagnosis must be deferred until longitudinal observation or a more accurate history is available.

Physical Examination

The often abrupt onset of symptoms, in many cases coupled with the lack of previous episodes, underscores the need for a toxicologic and medical evaluation.

A full Mental Status Examination helps establish the diagnosis. Mental status is likely to manifest as a neutral or blunted mood and affect. Evidence of paranoia, ideas of reference, delusions, and hallucinations are usually present. The patient is usually fully oriented with intact memory. A strong possibility of homicidal and even suicidal ideation exists.

An attempt should be made to elicit command hallucinations because these could drive a patient to hurt himself or herself, as well as others. Disorientation and difficulties with recall suggest an organic psychosis rather than a schizophreniform disorder.

 

DDx

Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following[1] :

  • Psychotic disorder due to another disease or its treatment

  • Substance- or medication-induced psychotic disorder

  • Delusional disorder

  • Schizotypal, schizoid, or paranoid personality disorder

  • Autism spectrum disorder

  • Disorders presenting in childhood with disorganized speech

  • Attention deficit hyperactivity disorder

  • Obsessive-compulsive disorder

  • Posttraumatic stress disorder

  • Traumatic brain injury

Differentials

Brief Psychotic Disorder

Bipolar Affective Disorder

Delirium

Depression

Schizoaffective Disorder

Schizophrenia

 

Workup

Approach Considerations

The Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) notes that for schizophreniform disorder, as for schizophrenia, there are currently no specific laboratory or psychometric tests.[1] However, laboratory tests, including a complete blood count (CBC), measurement of electrolyte concentrations, drug screening, and thyroid studies, may help rule out other conditions that can cause the symptoms.

Neuroimaging, neuropathologic, and neurophysiologic research has detected abnormalities in multiple brain regions. For example, schizophreniform disorder and schizophrenia may be associated with a decrease in right frontal white-matter volume in the early stages of disease.[12] However, none of these findings are diagnostic.

 

Treatment

Approach Considerations

Treatment may involve psychotherapy, family and social-educational therapies, and pharmacotherapy. The general aims of treatment are as follows:

  • To protect and stabilize the patient

  • To minimize the psychosocial consequences

  • To resolve the target symptoms with minimal adverse effects

Patients who may be likely to harm themselves or others should be hospitalized. This will allow a complete diagnostic evaluation and help ensure the safety of both patients and others. A supportive environment with minimal stimulation is most helpful.

As improvement progresses, help with coping skills, problem-solving techniques, and psychoeducational approaches may be offered to patients and their families. Patients may benefit from a structured intermediate environment (eg, a day hospital) during the initial phases of their return to the community.

According to Stromgren, electroconvulsive therapy (ECT) has been helpful in treating brief reactive psychoses, but in the setting of schizophreniform disorder, it is generally reserved for medication-resistant cases.[13]

Compton described barriers to treatment after the first psychotic episode, including inadequate remission of paranoia, impaired insight, and involvement with the criminal justice system between discharge from the hospital and the first outpatient appointment.[14] Strong family support appeared to be an important facilitator of treatment engagement during the first several months of outpatient treatment. Various other potential barriers to treatment, such as involuntary status at the time of hospital discharge, must also be considered.

Psychotherapy

Virtually all psychotherapeutic treatment modalities used in the treatment of patients with schizophrenia may be helpful in treating patients with schizophreniform disorder. Insight-oriented therapy is not indicated in patients with schizophreniform disorder, because these patients have limited ability to explore and may also be in denial.

Patients may experience a high degree of distress related to the onset of symptoms. Both supportive and educational approaches may help patients manage feelings of turmoil or distress. Group psychotherapy may be helpful; however, patients with schizophreniform disorder who are concerned about their prognosis may become frightened in groups where they are mixed with patients who have chronic schizophrenia. Thus, care must be taken in the formation of therapy groups.

Family and Social-Vocational Therapies

Treatment of patients with schizophreniform disorder frequently involves working with family members and significant others. The family therapy strategies used in working with the families of patients with schizophrenia are highly appropriate for patients with schizophreniform disorder and their families.

In view of the variable course of schizophreniform disorder, brief treatments with clear goals may be helpful initially, though therapeutic strategies must remain flexible to allow for the transition to longer-term treatments for patients who progress to schizophrenia. Similarly, social-vocational function may be preserved in patients with schizophreniform disorder. However, in patients exhibiting impairments in these areas, rehabilitative strategies similar to those described for patients with schizophrenia are appropriate.

Pharmacotherapy

Pharmacotherapy for schizophreniform disorder is similar to that for schizophrenia.[15] At present, atypical antipsychotics (eg, risperidone, olanzapine, quetiapine, and ziprasidone) are commonly used. Dosing strategies appear to be similar to recent approaches to treating patients with schizophrenia, which emphasize the use of minimal but effective doses.

Adequate treatment or prophylaxis of adverse extrapyramidal effects is critical to patient tolerance of neuroleptic treatment and to medication therapy compliance. Neuroleptic-resistant psychosis in patients with schizophreniform disorder may be managed through approaches similar to those used in patients with schizophrenia, including adjustment of the neuroleptic dose, addition of lithium, or addition of anticonvulsant agents and older typical antipsychotics.

Antidepressants may be helpful for mood disturbances associated with schizophreniform disorder, but care must be taken to monitor for possible exacerbations of psychotic symptoms.

Additional antipsychotic agents that have been used to treat schizophreniform disorder include the following:

  • Aripiprazole - Unlike its predecessors, this agent is a partial agonist at the dopamine receptors

  • Paliperidone - This agent is a major active metabolite of risperidone and the first oral agent that can be given once daily

  • Asenapine - Starting and recommended dose is 5 mg sublingually twice daily, not to exceed 10 mg sublingually twice a day

  • Iloperidone -– The initial dosage is 1 mg orally twice daily; this is titrated upward daily to reach the target dosage of 12-24 mg/day by day 7 (orthostatic hypotension is the dose-limiting adverse effect)

  • Lurasidone - Starting dose of 40 mg daily with at least 350 calorie of nonliquid food is an effective dose, not to exceed 160 mg daily maximum

Ziprasidone is available in injection form to help control acute psychosis; aripiprazole is also now available as an injection. These injections are less likely to cause acute extrapyramidal side effects.

Sajatovic et al concluded in one study that both risperidone and quetiapine improved scores on the Hamilton Depression Rating Scale (HAMD), though quetiapine yielded greater improvement than risperidone did in all patients.[16]

Emsley, in an international, multicenter, double-blind study conducted on 183 patients who had a first psychotic episode and were treated with flexible doses of risperidone or haloperidol for 6 weeks, found that 63% of patients treated with risperidone and 56% of those treated with haloperidol were clinically improved (350% reduction in Positive and Negative Syndrome Scale [PANSS] total scores).[17] Risperidone was tolerated better than haloperidol was.

Post hoc analysis indicated that low dosages of these antipsychotics were efficacious in some patients.[17] Other study findings also suggested that low antipsychotic dosages may be required for patients with a first psychotic episode. To optimize therapy for these patients will require trials that are specifically designed to compare low antipsychotic dosages with high dosages.

In a study examining patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment, Sanger et al found olanzapine to have a better risk-benefit profile than haloperidol in this population.[18] They concluded that because of advantages in safety and efficacy, atypical antipsychotic agents (eg, olanzapine) should be considered a preferred option for managing first-episode psychosis.

The clinical trial carried out by Sanger et al involved a subpopulation of first-episode patients selected from a pool of patients who were diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder.[18] The duration of the patients’ current psychotic episodes had to be 5 years or less, and the patients had to be aged 45 years or younger at the onset of their first psychotic symptoms.

 

Medication

Medication Summary

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.

Antipsychotics

Class Summary

Antipsychotic agents ameliorate psychosis and aggressive behavior.

Haloperidol (Haldol)

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 (Risperdal, Risperdal Consta)

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 (Zyprexa)

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 (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 (Seroquel)

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 (Geodon)

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 (Abilify)

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 (Fanapt)

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 (Invega)

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 (Latuda)

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.

Asenapine maleate (Saphris)

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.

Antimanic agents

Class Summary

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 (Lithobid)

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

Class Summary

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 (Prozac)

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 (Zoloft)

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 (Paxil)

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 (Luvox CR)

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 (Celexa)

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 (Lexapro)

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.

Anticonvulsants, Other

Class Summary

Some anticonvulsants work as mood stabilizers to correct the mood imbalance associated with bipolar disorder.

Valproic acid and derivatives (Depakote, Depakene, Depacon, Stavzor)

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 (Trileptal, Oxtellar XR)

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 (Tegretol, Carbatrol, Epitol, Equetro)

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.