Doses Of Neuroleptics Research Articles

Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder

Background: Borderline personality disorder (BPD) has long defied definitive treatment. Such failure is reflected in repeated suicidal crises, often associated with dysphoric symptoms of a chronic fluctuating nature, whose labile intermittent character does suggest a subthreshold bipolar depressive mixed state. For all these reasons, we hypothesized that the anticonvulsant lamotrigine, touted to be a mood stabilizer with antidepressant properties, might be uniquely beneficial for these patients. Methods: From a base rate of about 300 patients in a community mental health center, we identified eight patients meeting seven or more of the DSM-IV criteria for BPD without concurrent major mood disorders. All patients presented with history of severe suicidal behavior, hostile depression and/or labile moods, stimulant and alcohol abuse, as well as multiple unprotected sexual encounters; one patient was actually HIV positive. All had failed previous trials with different antidepressants and mood stabilizers. All current medications were gradually withdrawn – and when necessary – patients kept on a low dose of a conventional neuroleptics for a few weeks, while lamotrigine was being gradually introduced in 25-mg weekly increments until the patient responded (up to 300 mg/day maximum). Results: Consistent with previous work by us and others, bipolar family history could be documented in three of eight BPD patients, and worsening on antidepressants in four of eight, providing indirect support to our conceptualization of BPD as a bipolar variant. One patient developed a rash on 25 mg and was dropped from the lamotrigine trial, while another patient was noncompliant. Three who failed lamotrigine, subsequently responded, respectively, to sertraline, lithium–thioridazine combination, and valproate. The remaining three patients showed a robust response to lamotrigine, ranging from 75 to 300 mg/day: their functioning jumped from a mean baseline DSM-IV GAF score in the 40’s to the 80’s during 3–4 months. Among all responders impulsive sexual, drug-taking and suicidal behaviors disappeared and no longer met the criteria for BPD. At an average follow-up of 1 year, they no longer meet criteria for BPD. Limitations: Open uncontrolled results on a small number of patients in a tertiary care center may not generalize to BPD patients at large. Conclusions: Overall, the BPD response to pharmacotherapy in the present case series was 75%. The fact that five of six pharmacotherapy responders required mood stabilizers, argues against the prevalent view that the depressions of borderline patients belong to unipolarity. Of BPD patients who completed the trial, 50% achieved sustained remission from their personality disorder with lamotrigine monotherapy. The dramatic nature of the response in patients refractory to all previous medication trials and maintenance of a robust response over 1 year, argue against a placebo effect. Controlled systematic investigation of lamotrigine in BPD is indicated.

D(2)- and 5-HT(2) receptor occupancy in high-dose neuroleptic-treated patients.

Individual schizophrenic patients are sometimes reported to benefit from unusually high doses of neuroleptics. Such patients may have poor drug penetration into the brain or ultra-rapid metabolism. Alternately, very high doses may be required to induce occupancy of 5-HT(2) receptors, which have been suggested as mediators of atypical effects. Five schizophrenic patients treated with high doses of fluphenazine decanoate (100-250 mg/wk) and adjunct medications were examined with positron emission tomography and [(11)C]raclopride to measure D(2) receptor occupancy and [(11)C]NMSP to measure 5-HT(2) receptor occupancy. All patients were rated globally as 'markedly' to 'severely' ill and had high scores on all subscales of the Positive and Negative Syndrome Scale for schizophrenia. However, according to retrospective clinical evaluation, there was improved social function and reduced distress following high-dose treatment, an effect that deteriorated after previous explorative dose reduction. Extrapyramidal symptoms were modest. D(2) receptor occupancy was very high (89-97%). 5-HT(2) receptor occupancy was also high (76-105%). Plasma concentrations of fluphenazine were 5-37 nm. No patient had a cytochrome P450 CYP2D6 genotype associated with ultra-rapid drug metabolism. The findings suggest almost complete saturation of D(2) receptors, and do not support poor drug availability in the brain as the basis of the apparent high-dose requirement. The high 5-HT(2) receptor occupancy may have contributed to the apparent clinical improvement and modest degree of EPS. However, it is likely that the treatment used also induced occupancy of other neuroreceptors.

Caffeine and schizophrenia.

Although the database is small and not completely consistent, it appears that patients with schizophrenia have high caffeine intakes. The reasons are unclear. In nonhumans, caffeine enhances the effects of dopamine, which might be expected to worsen positive symptoms and improve negative symptoms of schizophrenia and worsen tardive dyskinesia. Eliminating caffeine among patients with schizophrenia does not appear to make them better or worse. Acute intake of large amounts of caffeine may increase psychoses and hostility. However, those who chronically use large amounts of caffeine may develop enough tolerance that these adverse effects do not occur, but whether this conjecture is true has not been tested. Interestingly, persons with schizophrenia do not develop anxiety at high doses of caffeine. Although there was initial concern that caffeine might inactivate liquid doses of neuroleptics, the clinical significance of this concern is unclear. On the other hand, caffeine might increase the level of clozapine, and more research in this area is needed.

Inhibitory effect of smoking on event-related potentials in schizophrenic patients: Comparison with healthy subjects

1. 1. A prior study demonstrated that the P300 peak amplitude of event-related potentials increased during acute withdrawal and smoking resumption in healthy subjects. Here the authors measured the P300 components in schizophrenic patients under similar conditions and compared them to normal controls. 2. 2. The P300 amplitude and area negatively correlated with the daily nicotine intake. 3. 3. The P300 amplitude and area were reduced by smoking resumption following overnight abstinence. 4. 4. The P300 components did not correlate significantly with the Brief Psychiatric Rating Scale or the equivalent neuroleptic dosage. 5. 5. The inhibitory effect of smoking was prevented by pretreatment with nicotine gum. 6. 6. In schizophrenics and healthy subjects, the chronic effects of smoking were similar. However, acute abstinence and smoking resumption decreased the P300 amplitude in schizophrenic patients but increased the amplitude in normal subjects. These results suggest that nicotine differentially affects arousal in schizophrenic patients and healthy subjects.

Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case–control study

Background: Pharmacologic and clinical risk factors for neuroleptic malignant syndrome have been suggested. High neuroleptic dose, rapid dosage increase, and parenteral administration were identified as risk factors in a case–control study; however, there are limited data regarding potential clinical risk factors. Methods: To examine potential clinical risk factors, we conducted a case–control study, comparing 12 cases to 24 controls, all treated with neuroleptics at our center. In addition to examining previously postulated pharmacologic risk factors, we also assessed for presence of psychomotor agitation, confusion, disorganization, and catatonia. Results: Significant differences were found between cases and controls for psychomotor agitation, confusion, disorganization, catatonia, mean and maximum neuroleptic dose, parenteral neuroleptic injections, neuroleptic dose increase within 5 days of the episode, magnitude of neuroleptic dose increase from initial dose, and extrapyramidal signs. Conclusions: This study demonstrated that psychopathological features such as psychomotor agitation, confusion, disorganized behavior, and catatonia may be risk factors for the neuroleptic malignant syndrome, in addition to pharmacologic risk factors and extrapyramidal signs, including akathisia. In clinical practice, careful monitoring for prodromal signs of neuroleptic malignant syndrome is required during neuroleptic treatment of patients with psychomotor agitation, confusion, and/or disorganization, while in the presence of catatonia these drugs should be avoided.

Change in plasma prolactin and clinical response to haloperidol in schizophrenia and schizoaffective disorder

There has been a long-standing interest in plasma prolactin as a potential in vivo indicator of blockade of tuberoinfundibular D 2 dopamine receptors. Potential relationships between prolactin response and neuroleptic treatment have been obscured by the use of high doses which have caused prolactin to plateau. With lower doses of neuroleptic now commonly in use, prolactin may be more valuable as a correlate of clinical response. In this study, 23 acutely exacerbated schizophrenic and schizoaffective patients were washed out for at least 6 days and were then treated with haloperidol to achieve fixed low to moderate plasma levels under double-blind conditions. Clinical response, plasma prolactin, and haloperidol plasma levels were measured weekly for 3 weeks. Clinical symptoms at endpoint were related to both prolactin change and final prolactin level during haloperidol treatment. Specifically, fewer symptoms at endpoint were associated with a greater increase in prolactin over time and a higher prolactin level at endpoint. Thus, prolactin increase caused by low to moderate doses of haloperidol may be a correlate of endpoint symptomatology. As lower doses of typical neuroleptics are now in use, prolactin response as a predictor of clinical response may have more clinical utility. Further study of prolactin and clinical response to typical neuroleptics should focus on low neuroleptic doses.

Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.

Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress. CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale. Tardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity. These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.

Neuroleptics in progressive structural brain abnormalities in psychiatric illness

Progressive abnormalities have been reported in schizophrenic patients. We did a prospective, longitudinal study of brain structure. 31 drug-naive psychotic patients underwent computed tomography (CT) at first admission to hospital and after 5 years of illness. We obtained written informed consent from all patients. A radiologist masked to the patients’ identities and diagnoses, date of scans, and the nature of the study compared the first and second CT scans. Brain atrophy was assessed on a visual scale, on which 0–1 meant no changes or dubious atrophy and 2–3 meant moderate or severe atrophic changes. After 5 years of illness, we found significant progression of frontal atrophy in 21 schizophrenic patients, compared with nine consecutively included healthy volunteers. We saw progressive frontal atrophy in ten non-schizophrenic patients, but to a lesser degree. During follow-up, schizophrenic patients recieved a median of 172 040 mg (range 19 540-928 450) neuroleptic medication (chlorpromazine equivalents). Seven nonschizophrenic patients received a median of 20 780 mg (range 678-141 596). The only atypical neuroleptic used was clozapine, administered to three patients, always in high doses and in combination with traditional neuroleptics. Patients were thought to have a chronic, non-remittent course of illness if all psychiatric records described a state of permanent psychosis, and if they were psychotic at the time of the reinvestigation. Some patients were described as remitted, but if in long interviews they showed firm delusive systems that seemed to be integrated but not necessarily overt parts of their lives, and if they were judged to be permanently deluded, despite their records, they were classified as non-remittent. This classification was made without knowledge of the results of the CT scans. Nine schizophrenic patients (eight men and one woman) had been continuously psychotic during follow-up. At reinvestigation, non-remittent patients had significantly higher ratings for psychopathology (SANS and SAPS) than remittent patients. Because of the small sample, we did exact tests in a logistic regression analysis with LogXact, adjusted for sex, course of illness, (remission/non-remission), diagnosis, and neuroleptic load. Course of illness and diagnosis had no significant impact on the development of frontal atrophy. Sex was significant (p=0·035) if course of illness was not included into the model, but sex became non-significant (p=0·138) if course of illness was included. Neuroleptic load was significant whether sex was included or not (p=0·013 and 0·0003, respectively). The estimated risk of atrophy increases by 6·4% for each additional 10 g neuroleptic drug. Non-remittent patients received a higher neuroleptic dose than remittent patients, but the model was corrected for this interaction. Association has been shown between frontal atrophy or aplasia and non-respondence to antipsychotic drugs, and neuroleptic side-effects as tardive dyskinesia and akathisia have been associated with wider sulci. These studies do not include neuroleptic load as a possible explanatory factor for the anormalities found. Traditional neuroleptics have been shown to affect brain structure because they enhance the volume of basal ganglia, but the potential impact of neuroleptics, on frontal cortex, for example, is not known. Factors causing progression of brain atrophy have not yet been identified. Our study showed an unexpected effect of

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia.

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-III-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Relationship between auditory P300 amplitude and age of onset of schizophrenia in older patients

Auditory P300 amplitude reductions are well-established in young adults with schizophrenia. Little is known, however, regarding the P300 in older schizophrenia patients, especially those with late onset. We studied 28 middle-aged and elderly (mean age=62.7 years) patients [14 with early onset schizophrenia (EOS) and 14 with late onset schizophrenia (LOS)] and 14 normal comparison (NC) participants using an auditory oddball paradigm. Event-related potentials were recorded from 15 scalp electrodes and six non-scalp sites. There were no significant differences between EOS and LOS groups in neuroleptic dosage, symptom severity, reaction times, target-detection accuracy, or N100 and N200 ERP measures. The EOS, but not the LOS, group had significantly smaller auditory oddball P300 amplitudes than the NC group. Twelve of the 14 LOS patients had P300 amplitudes in the normal range. Smaller P300 amplitudes were associated with earlier age of onset ( r=0.48), longer duration of illness ( r=−0.49) and more severe alogia ( r=−0.50). We conclude that P300 abnormalities in schizophrenia may be a marker for a disease subtype with early onset and more severe information-processing deficits.

Tardive dyskinesia and debrisoquine 4-hydroxylase (CYP2D6) genotype in Japanese schizophrenics

Previous studies have shown that many neuroleptics are metabolized by debrisoquine 4-hydrolase (CYP2D6), which exhibits genetic polymorphisms. In Oriental populations, poor metabolizers (PMs) with a lack of CYP2D6 activity are rare, although the CYP2D6 * 10 allele, which is associated with decreased CYP2D6 activity, is commonly found. The authors examined the relationship between tardive dyskinesia (TD) and CYP2D6 polymorphisms, including the CYP2D6 * 10 allele. Subjects consisted of 100 Japanese schizophrenics. TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Genotyping for the presence of the CYP2D6 *3, CYP2D6 *4 and CYP2D6 *10 alleles was performed using allele-specific PCR amplification and endonuclease digestions. The frequency of the CYP2D6 *10 allele was 0.52, and only one allele showed the PM genotype. There was a significant difference in the allelic distribution of CYP2D6 *10 between subjects with and without TD. We also found significant genotypic and allelic associations with dichotomized total AIMS scores of 6 or more (moderate or severe abnormal movements) and with scores of less than 6 (mild or no movements). After these associations were adjusted for confounding variables (gender, age, duration of illness and neuroleptic dose) by regression analysis, the CYP2D6 *10 genotype showed significant association with the total AIMS score, and a modest association with TD occurrence. These results indicate that the CYP2D6 *10 genotype may play a role in the development of moderate or severe abnormal movements.

Negative symptoms in schizophrenia: neurobiological models and treatment response.

Evidence from lesioning studies and neuroimaging has linked negative symptoms to dysfunction of the prefrontal cortex, the limbic system, and the basal ganglia. Although such symptoms have been most strongly associated with dopaminergic hypoactivity in the prefrontal cortex, other neurotransmitters including norepinephrine, serotonin, and the excitatory amino acids may also play a role. In some patients moderate doses of conventional neuroleptics clearly improve negative symptoms; the response of such symptoms is relatively greater with clozapine and probably with certain serotonin-dopamine antagonists. Recent studies demonstrating improvement of negative symptoms when conventional neuroleptics are augmented with selective serotonin-reuptake inhibitors or with agents active at the glycine-modulatory site of the glutamatergic N-methyl-D-aspartate receptor complex suggest that further amelioration of primary negative symptoms may be possible through pharmacological strategies involving multiple neurotransmitter systems.

Case Study: Worsening Tourette's Disorder or Withdrawal Dystonia?

This case report focuses on withdrawal dystonia, a movement disorder associated with neuroleptics. Its occurrence in a patient with Tourette's disorder complicated the clinical picture. A misinterpretation of the symptoms led to ineffective management of the movement disorder. The presence of increased blinking with facial pain, dystonic movements, and other facial movements at each neuroleptic dose reduction pointed toward withdrawal dystonia rather than toward a worsening of Tourette's disorder. Implications for diagnosis and treatment are discussed.

Acute Neuroleptic Treatment in Elderly Patients Without Dementia

Low doses of neuroleptics are the standard for treating psychosis in elderly patients because of concern about inducing adverse effects. The authors found that fixed, low-dose neuroleptic treatment (0.15 mg/kg/day) for 10 days resulted in low perphenazine levels and low rates of acute response (25%) in elderly patients with primary psychotic illness (without dementia). Increase in initial dose did not speed acute response and induced adverse effects that were absent or minimal with low-dose treatment. With higher-dose treatment, drug blood levels rose disproportionately, and level-to-dose ratios were higher than those observed in non-elderly adults. Naturalistic follow-up suggested that response may take longer to develop than in non-elderly adults and that low doses for a longer duration may provide effective treatment.

Influence of Neuroleptics on Cytotoxic Activity of Rat Natural Killer Cells

The aim of the study was to evaluate the in vivo and in vitro effects of three neuroleptics (chlorpromazine, haloperidol, and sulpiride) on the activity of rat spleen NK cells. In the in vivo experiment, rats were injected with different intraperitoneal doses of neuroleptics given once, for 14 or 28 days. In the in vitro experiment rat spleen NK cells were cultured in medium containing two different concentrations of neuroleptics for three days. The cytotoxic activity of NK cells was evaluated by measuring 51Cr release from YAC-1 target cells after 4-hour incubation. We also measured, using fluorescein-labelled anti-NK monoclonal antibody, the percentage of NK cells in the splenocyte population before and after single intraperitoneal injections of neuroleptics. In the in vitro experiment, both haloperidol (1×10−5M and 1×10−6M) and sulpiride (1.5×10−3M and 1.5×10−4M) induced a statistically significant decrease in the cytotoxic activity of NK cells. The lower dose of chlorpromazine (6×10−6M) decreased the cytotoxic activity of NK cells, while the higher dose (6×10−5 M) did not. In the in vivo experiment, both single and repeated doses of chlorpromazine (2 mg /kg /day), haloperidol (0.5 mg/kg/day) and sulpiride (50 mg/kg/day) increased NK cell activity. That effect reflected an increase in NK cell activity but not in the number of NK cells. The study has shown that the immunomodulatory effect of neuroleptics on NK cell activity depends mainly on drug concentrations and experimental conditions.

Relationship of gender and menstrual status to symptoms and medication side effects in patients with schizophrenia

Schizophrenic outpatients (62 females, 59 males) were evaluated to examine the relationships between menstrual status, gender, clinical measures of psychopathology and drug side effects. Menstrual status was determined for 55 female patients. Blood from 44 female subjects, drawn before the AM dose of neuroleptic, was assayed for prolactin concentrations. In 27 premenopausal women (age<45 years), six (22%) reported irregular menses and one (4%) reported amenorrhea. Women with irregular menses did not differ in their prolactin levels or neuroleptic dose, from women with regular menses. Amenorrheic women (n=22) were significantly older than men (n=59) and menstruating women (n=33). After controlling for age, menstruating women did not differ in clinical measures of psychopathology, drug side effects, or neuroleptic dose compared to amenorrheic women or men. Comparison of 15 age-matched pairs of menstruating females and amenorrheic females revealed significantly lower levels of akathisia and depression in the menstruating group and a trend towards lower serum prolactin concentrations (P=0.08). In female subjects, prolactin levels correlated significantly with neuroleptic dose (r=0.36, P<0.005). Our results only partially support hypothesized relationships between menstrual status, prolactin levels and neuroleptic effects and serve to emphasize the importance of controlling for age when comparing these clinical variables.

A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures.

Cross-sectional neuroanatomical studies have reported abnormalities in schizophrenia that relate to disease variables. Longitudinal neuroimaging investigations that integrate anatomical, clinical, and neurobehavioral measures may help clarify the pathogenesis of schizophrenia. Magnetic resonance brain imaging and neurobehavioral studies were conducted at baseline and after 30.63 +/- 12.92 months (mean +/- SD) in 40 patients with schizophrenia (23 men and 17 women) and 17 healthy controls (13 men and 4 women). The schizophrenia group included 20 first-episode and 20 previously treated subjects. Volumes of whole-brain, cerebrospinal fluid, and frontal and temporal lobes were measured. The severity of negative and positive symptoms was assessed, medications were monitored, and neurobehavioral functioning in 8 domains was evaluated. Both first-episode and previously treated patients had smaller brains and frontal and temporal lobes than controls at intake. Longitudinally, reduction in frontal lobe volume was found only in patients, whereas temporal lobe reduction was also seen in controls. The association between volume reduction and symptom changes differed between patient groups, but volume reduction was associated with decline in some neurobehavioral functions in both groups. Exploratory analysis suggested that neuroleptic dose is correlated with changes in all 3 domains. The existence of neuroanatomical and neurobehavioral abnormalities in patients with first-episode schizophrenia indicates that the brain dysfunction occurred before clinical presentation. However, there is also evidence of progression, in which anatomical changes may affect some clinical and neurobehavioral features of the illness in some patients.

An audit of the use of high dose neuroleptics in treating schizophrenia

An audit of the use of high dose neuroleptics in treating schizophrenia

The management of severe psychiatric disorder: A comparison of the use of neuroleptic medication in two intensive therapy units

Concern over the use of high dose neuroleptic medication has led to the introduction of guidelines for prescribing. This is of particular importance in the treatment of patients with severe psychiatric disorder. This study evaluates how physical security of the ward relates to prescribing in two close supervision units. A prospective analysis of 93 consecutive admissions to two wards, one locked and the other open, was undertaken. Data included patient characteristics, diagnosis and medication received. There was no difference in total neuroleptic dosage between the two wards, but mean daily dose (2,108 mg chlorpromazine equivalent) exceeded maxima specified in guidelines. In the early stages of admission, the open ward used higher regular doses, whereas the locked ward prescribed more on an as required basis. The high incidence of absconding from the open ward must be considered against the more custodial environment of the locked ward. The wider use of chlorpromazine equivalence calculations is recommended.

Neuroleptic dose reduction in older psychotic patients

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropyschological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics ( n=19) or maintained on neuroleptics ( n=22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in the group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over the time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.