Lupus Cerebritis Refractory to Guideline-Directed Therapy: A Case Report.

Systemic lupus erythematosus is an autoimmune disease that affects multiple organs and organ systems, subsequently requiring an elaborate regimen for management. We present the case of a 63-year-old female who developed unrelenting symptoms of drug-induced lupus, which persisted even after the offending agent was withdrawn, unmasking her underlying systemic lupus erythematosus. She continued to develop neuropsychiatric symptoms, including mania and hallucinations, which complicated the management of her disease. After exhausting the bank of anti-inflammatory and immunomodulators recommended by current guidelines, we found that a combination of rituximab infusions with thiothixene, an antipsychotic agent, significantly improved our patient's neuropsychiatric symptoms. Further research should be conducted to determine the efficacy of rituximab in the treatment of resistant lupus cerebritis, and to validate the use of thiothixene in the management of neuropsychiatric symptoms secondary to lupus.

Thiothixene in the Management of Delirium: A Case Series.

BACKGROUND: Pharmacologic strategies are often required to help manage agitated patients with delirium. First-and second-generation antipsychotic medications (such as haloperidol, quetiapine, and olanzapine) are commonly used. OBJECTIVE: On the psychiatric consultation service in our hospital, thiothixene has been used based on its favorable potency, sedative, and cost profiles. Little has been written about the utility of this drug for management of delirium. METHODS: We reviewed our experience with thiothixene in this setting using pharmacy records to identify patients who received at least 1 dose between July 2011 and March 2014. We scrutinized the relevant medical records (n = 111) and recorded the following data: age, sex, medical diagnoses, signs and symptoms of delirium, dosing of thiothixene, and response to thiothixene in terms of both apparent benefit as well as side effects. RESULTS: Resolution or improvement was documented in 78% of patients and good tolerability in 82% of patients. CONCLUSIONS: Although further data from a randomized, controlled trial would be ideal, our experience suggests that thiothixene could be a safe and effective pharmacologic treatment for agitation and psychosis due to delirium.

Full circle-old drugs prove more beneficial than newer agents for schizophrenia: a case report.

A 55-year-old female with a diagnosis of schizophrenia currently resides in an assisted living facility in a large metropolitan suburb. For approximately 25 years, the patient was relegated to a life of poor symptom control and social adjustment, largely due to nonadherence, relapse, and rehospitalization. The patient experienced a trial-and-error approach to drug therapy, which resulted in reliance on the older or first generation agents for symptom improvement. This case supports the assertion that the second-generation or atypical antipsychotics used to treat schizophrenia are no better than older drugs in terms of efficacy or tolerability.

Network-assisted investigation of antipsychotic drugs and their targets.

Antipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network-based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a drug-gene network and a drug-drug interaction network. Through drug-gene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drug-drug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network-assisted investigation of antipsychotics demonstrates that network-based analysis is useful for uncovering the molecular actions of antipsychotics.

Adjunctive quetiapine decreases symptoms of tardive dyskinesia in a patient taking risperidone.

Tardive dyskinesia is a potentially permanent and disfiguring side effect associated with the use of conventional, or first generation, antipsychotics. Quetiapine is a second generation antipsychotic with transient dopamine receptor occupancy, a property shared with clozapine. Quetiapine was administered to a patient who had persistent choreoathetoid movements that developed during treatment with conventional antipsychotics and remained unimproved during longterm treatment with risperidone. During 10 weeks of monotherapy with quetiapine, his Abnormal Involuntary Movement Scale score fell from 11 to 3. He was subsequently switched back to risperidone and his movements returned. The addition of quetiapine to his risperidone regimen once again resulted in a decrease of his tardive dyskinesia symptoms. The mechanism by which quetiapine improved tardive dyskinesia symptoms in this patient is not known, but differential treatment effects between the novel antipsychotics may exist. Controlled trials of quetiapine in the treatment of tardive dyskinesia should be pursued.

Effects of antipsychotic treatment on polysomnographic measures in schizophrenia: a replication and extension.

OBJECTIVE: The authors sought to replicate and extend previous observations of improvement in some EEG sleep measures during the course of antipsychotic treatment in schizophrenia patients. METHOD: Fourteen medication-free patients with schizophrenia underwent 2 nights of sleep EEG monitoring before and after 3-4 weeks of treatment with clinically determined doses of haloperidol or thiothixene. RESULTS: Measures of sleep continuity improved consistently. REM latency increased, although five of 14 patients continued to exhibit short REM latencies (less than 60 minutes). Stage 3 sleep increased during neuroleptic treatment, while stage 4 sleep did not change. CONCLUSIONS: These data demonstrate partial improvement of some but not all EEG sleep measures in schizophrenic patients through the course of neuroleptic treatment. They suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities, while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.

The effect of antipsychotic medication on relative cerebral blood perfusion in schizophrenia: assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography.

Functional neuroimaging studies in schizophrenia have often been confounded by various factors including medication status. To explore the effects of antipsychotic medications on relative regional cerebral perfusion, we scanned a group of 33 persons with schizophrenia twice, while receiving a stable dose of antipsychotic and after being off antipsychotics for 3 weeks, using technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography (Tc-99m HMPAO-SPECT. We found that antipsychotic significantly increased the mean relative cerebral perfusion in the left basal ganglia. Additionally, patients receiving thiothixene (n = 9) had a significantly greater increase in relative cerebral perfusion in the basal ganglia than patients receiving haloperidol (n = 12). These findings indicate that antipsychotics lead to regional increases in cerebral perfusion and that antipsychotic status must be controlled for in functional neuroimaging studies. Functional neuroimaging techniques such as SPECT may be useful in furthering our understanding of the mechanism of antipsychotics.

Tardive tourettism after exposure to neuroleptic therapy.

A case of neuroleptic-induced adult-onset tardive tourettism is presented with video documentation. After prolonged neuroleptic therapy, the patient developed motor and vocal tics at 36 years of age. The tics were identical to those seen in childhood-onset Tourette's syndrome. These cases are rare and have been considered by some to represent tardive akathisia. Previous reports of tourettism after neuroleptic therapy are reviewed.

Distractibility in schizophrenia.

This study examined the effects of neuroleptic medication on the allocation of attentional resources to distracting stimuli in patients with schizophrenia. Twenty-five patients were tested twice (medication-free and after medication stabilization) on the Identical Pairs versions of the Continuous Performance Test under both distraction and no-distraction conditions. Sixteen patients were chronically ill adults and nine patients were young neuroleptic-native patients in the early stages of illness. Results indicated that neuroleptic treatment did not improve distractibility for either group and that both groups were comparably distractible. These findings suggest that medication does not improve the misallocation of attention to distracting stimuli in patients with schizophrenia.

Case report: recurrent pseudocyesis in a male patient with psychosis, intermittent hyponatremia, and polydipsia.

This report describes a case of recurrent pseudocyesis in a man with psychosis, intermittent hyponatremia, and polydipsia. The pseudocyesis was documented on three separate occasions coinciding with bouts of acute hyponatremia and rapid weight gain stemming from ingestion of large amounts of water. In contrast, no pseudocyesis was elicited during intervening normonatremic states. Abdominal distention, neuropsychological deterioration, and worsening of psychosis during acute hyponatremia are considered as contributing factors to the pseudocyesis.

Chlorpromazine-induced psychosis after brain injury.

Antipsychotic agents, most often used for treatment of schizophrenia, are sometimes prescribed for the agitated patient with an organic brain disorder. We report the case of a brain-injured patient who was prescribed chlorpromazine for agitation and who developed a delusional state while taking this antipsychotic agent. The emergence of this delusional state coincided with the exacerbation of certain cognitive deficits. Possible mechanisms for this phenomenon are discussed. Caution is advised when prescribing neuroleptics for patients with traumatic brain injury, especially those agents with significant cognitive side-effects or with a significant potential to precipitate seizures.

Ciprofloxacin-induced psychosis.

OBJECTIVE: To report a case of ciprofloxacin-induced psychosis and to discuss occurrence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this adverse reaction. DATA SOURCES: Case reports and review articles identified by MEDLINE. DATA EXTRACTION: Data from pertinent published sources were reviewed and abstracted. DATA SYNTHESIS: A 49-year-old man developed symptoms of severe psychosis concomitant with ciprofloxacin (250 mg bid) treatment. Central nervous system effects secondary to ciprofloxacin treatment are uncommon and usually consist only of minor dizziness or mild headache, although rare occurrences of seizures and hallucinations have been reported. The mechanism by which ciprofloxacin causes these adverse effects is not fully understood. It has been suggested that quinolones may produce an epileptogenic effect by inhibiting the binding of gamma-aminobutyric acid to its receptor sites in the brain. There is yet no explanation for the occurrence of hallucinations or psychosis. CONCLUSIONS: Caution should be exercised when using ciprofloxacin in the treatment of patients with personality abnormalities or symptoms of psychosis.

Response of negative symptoms of schizophrenia to neuroleptic treatment.

BACKGROUND: In view of the inconclusive reports in the literature about the response to neuroleptics of chronic schizophrenics with negative symptoms, the authors further evaluated this issue. METHOD: A sample of 30 ambulatory chronic schizophrenics meeting DSM-III-R criteria who had to a marked degree at least two negative symptoms of the five on the Scale for the Assessment of Negative Symptoms (SANS) received various therapeutic dosages of thiothixene for 3 months. The average dose was 26.75 mg/day. Subjects were periodically evaluated with the Brief Psychiatric Rating Scale, Negative Symptoms Rating Scale (a modified version of the SANS), and the Randt Memory Test. The time effect on treatment was calculated by repeated measures of analysis of variance. The relationship between the positive and negative symptoms was tested by an analysis of covariance. RESULTS: Both negative and positive symptoms improved with treatment. The negative symptoms tended to respond to treatment predominantly independently of the positive ones. At the end of the study, 63% (N = 19) of patients had improved moderately, 16% (N = 5) had improved slightly, and 20% (N = 6) had not improved. CONCLUSION: The data require further support from a long-term follow-up study that may show the extent to which these gains are maintained over time.

A single-case-study method for treating resistiveness in patients with Alzheimer's disease.

A single-case-study approach was used to identify the best medication for treating resistiveness to care in patients with moderately advanced dementia. The double-blind research design incorporated three medications, placebo washout periods, multiple baselines, frequent ratings by nurses of patients' resistiveness, and visual and statistical analysis of results to find the optimal drug, one that provided a stable response at a low dose. Six patients completed the trials. Thiothixene was more effective than oxazepam and diphenhydramine. Important features of the design were its avoidance of polypharmacy and high doses and its use of frequent ratings (each nursing shift) of patients' resistiveness. Although the single-case-study method is labor intensive, it can be beneficial when adapted for clinical use.