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.

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.

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.

Phototoxic properties of neuroleptic drugs.

BACKGROUND: Photo-induced eruptions are well-known adverse effects of some neuroleptic drugs, particularly chlorpromazine. OBJECTIVE: By a photohemolysis test we assessed in vitro the phototoxic properties of 12 phenothiazines (chlorpromazine, dixyrazine, fluphenazine, levomepromazine, perazine, perphenazine, promazine, promethazine, prothipendyl, thioridazine, trifluoperazine, triflupromazine) and 5 thioxanthenes (chlorprothixene, clopenthixol, flupenthixol, thiothixene, zuclopenthixol). METHODS: Human erythrocytes from 3 donors were incubated with the compounds and irradiated with light sources rich in UVA or UVB, respectively. Doses were up to 100 J/cm2 UVA or up to 1,600 mJ/cm2 UVB. Photo-induced hemolysis was calculated as percentage of complete hemolysis. RESULTS: Photo-induced hemolysis >10% due to radiation rich in UVA was found with chlorpromazine (maximal median: 98%), dixyrazine (100%), fluphenazine (84%), perazine (100%), perphenazine (100%), promazine (16%), promethazine (25%), prothipendyl (96%), trifluoperazine (100%), triflupromazine (76%), chlorprothixene (100%) and thiothixene (31%). UVB-rich radiation induced hemolysis only with chlorpromazine (73%), dixyrazine (45%) and perazine (60%). CONCLUSION: Most neuroleptics are strongly phototoxic in vitro indicating a potential risk for photo-induced reactions also to occur in patients treated with these drugs.

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.

A case report of venlafaxine toxicity.

Venlafaxine hydrochloride is a novel bicyclic antidepressant which inhibits the reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine. A 41-year-old female ingested 4.5 g venlafaxine, 500 mg diphenhydramine, 50 mg thiothixene and subsequently experienced severe central nervous system depression requiring intubation. She also developed elevated systolic and diastolic blood pressures and sinus tachycardia. The patient was decontaminated with gastric lavage and activated charcoal. She regained consciousness within a few hours and was extubated nine hours after ingestion. This case demonstrates that severe central nervous system depression may follow venlafaxine overdose.

Effects of medication on parotid salivary flow rates in an individual with dementia of the Alzheimer type.

Data available on the relationship between salivary function and specific drug therapy are sparse. We measured unstimulated and stimulated parotid salivary flow rates associated with the drug therapies. Our ancillary study design is an N = 1 double-blind randomized controlled trial in which the patient undergoes a series of treatment blocks of either placebo or active treatment. The purpose of the parent N of 1 study was to find the "best single drug" treatment for a resistive patient diagnosed with dementia of the Alzheimer type. This study demonstrates that thiothixene was associated with inconsistent effects on parotid flow. Oxazepam had no effect on his parotid function, and diphenhydramine hydrochloride had inconsistent but generally negative effects. The data also show that this individual with dementia of the Alzheimer type had lower baseline unstimulated and stimulated parotid salivary flow rates when compared with mean "normal" values; however, flow rates were above the lowest 10th percentile of "normal" volunteers.

Neuroleptic malignant syndrome: liability in nursing practice.

In the summer of 1991, the malpractice case Reyes v Houston International Hospital et al was settled for an amount in excess of $600,000. The case involved the psychiatric treatment received by Marjorie Reyes, a 27-year-old Latin-American mother of three, who was admitted to a psychiatric unit in late October 1986 with a diagnosis of atypical psychosis. Malpractice was charged because her treatment failed to meet any reasonably expected outcome for atypical psychosis. In fact, Reyes developed neuroleptic malignant syndrome (NMS) as a direct result of the antipsychotic medications she was administered. Her treatment outcome was nearly fatal and caused permanent, serious neurological disabilities. The litigation implicated the nursing care delivered in a psychiatric setting. This unfortunate situation illustrates general principles of legal liability in nursing practice as well as offers a unique opportunity to review NMS and to examine the specific implications for the assessment and evaluation of the side effects of antipsychotic medications. Additionally, methods of behavioral control, specifically as they relate to concepts concerning the use of medications, the importance of documentation, and the manner in which nurses plan care, were also addressed in the case. It is important for professionals to be familiar with general legal concepts and liabilities, the potential of the development of this serious side effect, and how clinical decisions regarding the administration of both routine and as-needed medications may incur legal accountability.

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.

Thiothixene pharmacokinetic interactions: a study of hepatic enzyme inducers, clearance inhibitors, and demographic variables.

Fifty-nine plasma thiothixene concentrations were measured in 42 patients as part of routine therapeutic drug monitoring. Data collection included concomitant medications, smoking history, and demographic variables. A retrospective analysis was performed to assess the effect of these parameters on oral thiothixene clearance. When groups of patients were categorized by concomitant medications (i.e., no interacting drugs, enzyme/clearance inducers, and enzyme/clearance inhibitors), thiothixene clearance was found to be significantly increased by enzyme inducing drugs (e.g., anticonvulsants) and decreased by clearance inhibiting agents (e.g., cimetidine). Tobacco smoking significantly increased the hepatic clearance of thiothixene within the no interactions and inhibitor groups, but not in the inducer group. Significantly more patients in the inducer group had nondetectable plasma concentrations of thiothixene than the other groups. When the entire patient population was dichotomized by age, patients less than 50 years old had a significantly greater mean clearance (48.2 +/- 37.8 liters/min) versus those greater than or equal to 50 (20.0 +/- 12.6 liters/min). Men in this cohort exhibited a significantly higher clearance (49.2 +/- 38.7 liters/min) than did the women (22.0 +/- 13.5 liters/min). By taking into account these potential sources of pharmacokinetic variability when monitoring plasma thiothixene concentrations, more appropriate dosing of thiothixene may be achieved. Controlled, prospective studies are needed to validate these findings.