Schizophrenic psychoses

Psychoses, when they occur, appear to be due to drug effect interacting with a vulnerable personality organization (Luisada 1978). Our experience has been that some adolescents with borderline personality disorders, as well as adolescents at risk of schizophrenic decompensation, may have this vulnerability. Although we do not have hard data to support the hypothesis that patients with PCP psychoses that are most resistant to treatment have the poorest long-term prognosis (Erard et al. 1980), our observations have been that persistence of symptoms of psychosis after the first 2 to 3 weeks of treatment often correlates with extended periods of impai rment. 

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

Toxic psychosis Several monoamine stimulants including cocaine are known to produce a temporary or even a lasting psychotic state after heavy use. Reviews of numerous clinical case reports have shown amphetamine to produce a chronic psychotic state, sometimes persisting for months after cessation. There appears to be a sensitization effect in this regard, because after recovery, psychotic states may recur with minimal use of amphetamine or alcohol. When compared to schizophrenic patients, people with amphetamine-induced psychosis demonstrate fewer negative symptoms (Boutros and Bowers 1996). 

In psychiatric practice, promazine is used in minor cases of psychomotor excitement in schizophrenics, in paranoid and manic-depressive conditions, for neurosis, alcoholic psychosis, and others. It is sometimes used in anesthesiological practice. The most common synonyms are propazine, trilafon, sparine, permitil, and others. 

Psychiatric patients Schizophrenic or paranoid patients may exhibit a worsening of psychosis with TCA therapy, and manic-depressive patients may experience a shift to a hypomanic or manic phase this may also occur when switching antidepressants and withdrawing them. In overactive or agitated patients, increased anxiety or agitation may occur. Paranoid delusions, with or without associated hostility, may be exaggerated. Reduction of TCA dosage and concomitant antipsychotic therapy may be necessary. 

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

In general, schizophrenic psychoses have to be treated by a multimodal approach including medication, psychotherapeutic interventions, and in chronic cases, rehabilitation. During the acute state of the psychosis, inpatient treatment and antipsychotic medication are required as the most important components. Drug treatment is the most important component during the first inpatient phase. 

Efficacy in short-term treatment. From studies in adult schizophrenia, it is evident that clozapine treatment has at least the same or superior antipsychotic effect, compared to typical antipsychotics. In some studies, clozapine was superior with regard to symptom reduction in severe and acute schizophrenic patients. As the guidelines do not allow the use of clozapine as a first-choice drug, most patients have been treated before with at least two atypical or typical antipsychotics. Only one controlled trial has assessed the efficacy of clozapine in child and adolescent psychiatry. In this study (Kumra et ah, 1996), clozapine was found to be superior to haloperidol in all measures of psychosis, and showed a striking superiority for both positive and negative symptoms. 

Given the available data, it is extremely important that clinicians evaluate patients with major depression for features of psychosis, because the failure to do so may result in inadequate treatment for the patient. A practical problem encountered by clinicians, however, is the subtlety of delusions. For example, it is not unusual in geriatric depression for patients to present with a somatic preoccupation that borders on delusional. These so-called near delusions may put the patient into the arena of psychotic depression. Some evidence exists that patients with depression with near delusions may respond more favorably to combinations of antidepressants and antipsychotics or ECT. Once the presence of both major depression and psychosis is determined, other psychotic disorders including bipolar disorder and schizophrenic spectrum illness must also be ruled out because this may influence long-term treatment decisions. 

SNA produces an acute psychosis with some similarity to that seen In schizophrenic disorders some users, this schizophrenialike... 

Erard et al.25a,43 believe that the psychosis Is a special form of an acute schizophrenic episode activated by the drug In some susceptible persons. Luisada estimated that 1-5% of the population may be susceptible (Luisada, P.V. personal comunicatlon). Although the Army volunteers were psychologically screened, preschizophrenic test subjects may have been Included. As noted, the psychotic reactions associated with SNA typically occur Immediately or soon after consumption of the drug. If serious mental consequences were not observed during the Immediate followup period or during the later Army tour of duty, It seems unlikely that a delayed SNA psychosis occurred. 

The target organs that may be involved in prolonged or delayed effects are the brain and the cardiovascular system. The mental effect consists of a transient or reversible psychosis, which may in rare instances result in activation of a schizophrenic process. The cardiovascular effects are postural hypotension and tachycardia. 

Amphetamine used at high doses can provoke a toxic syndrome ( amphetamine psychosis ) in healthy subjects that shows certain similarities to schizophrenic psychoses. Like cocaine, high-dose amphetamine is known to trigger a massive release of dopamine and noradrenaline from presynaptic sites and thus to produce a temporary excess supply of both neurotransmitters at the respective synapses. 

Even at smaller doses, amphetamine can exacerbate psychosis in schizophrenic patients, and similar symptom provocation may arise with other dopaminergic substances. 

Several studies investigated the outcome in schizophrenic patients before antipsychotics were available ( 25, 26 and 27) and generally found that an early onset of insidious symptoms, most characterized by negativity and a gradual deterioration into psychosis without clear precipitating events, was predictive of a poor outcome. These patients often demonstrated asocial and bizarre behavior during childhood and typically never married ( 28, 29, 30 and 31). 

Additional evidence comes from studies of increasing dopaminergic activity in patients with active psychosis. Small i.v. doses of methylphenidate (e.g., 0.5 mg/kg) can result in a marked exacerbation of an acute schizophrenic episode (18). By contrast, such doses usually do not produce psychotic symptoms in normal control... 

For many years, schizophrenia was divided into process (core) and reactive types. More recent investigations indicate that the reactive psychotic group has many affective, as well as schizophrenic features (e.g., family histories). This distinction is recognized in the DSM-IV ( 373) by such disorders as schizophreniform, schizoaffective, and brief reactive psychosis. 

Little work has been done on the drug treatment of schizophreniform or brief reactive psychosis. Flirschowitz et al. ( 374) further explored the range of lithium s efficacy by systematically treating patients with schizophrenic or schizophreniform disorders. They found that poor-prognosis schizophrenia rarely responded to lithium. 

---