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The purpose of this study was to determine if Second-Generation Antipsychotics (SGAs), relative to First-Generation Antipsychotics (FGAs), reduced either the length of stay (LOS) or number of re-hospitalizations of schizophrenic patients receiving treatment in a state psychiatric hospital. Medical records were compared for the periods 1991-1994 and 2001-2004 for three inpatient groups: those receiving FGAs, those receiving SGAs, and those switched from FGAs to SGAs. During both time periods, patients on FGAs had significantly shorter LOS than either those receiving SGAs or those switched from FGAs to SGAs. Therefore, inpatients receiving SGAs were hospitalized longer than those receiving FGAs. Conversely, once discharged, patients receiving SGAs were significantly less likely to be re-admitted than patients discharged on FGAs. The data suggest that some patients do benefit from SGAs and it may be cost-effective in the long-term, to determine when to utilize FGAs first and when to switch from the older to the newer agents.

Background: Concerns about the therapeutic and neurological benefits of Second Generation Antipsychotics (SGAs), and financial conflicts of interest and possible biases in the recruitment of research participants, prompted this “real world” study of antipsychotic effectiveness for schizophrenia in the naturalistic setting of a public psychiatric hospital.Method: Patients who gave informed consent were evaluated with the Brief Psychiatric Rating Scale and the Clinical Global Impression Scale. Neurological side effects were rated with the Simpson-Angus Scale, the Abnormal Involuntary Movement Scale, and the Barnes Akathisia Scale.Results: During the study there were 38 eligible patients out of a total 123 admissions, but only 10 gave consent. Baseline symptoms were moderate, with minimal neurological side effects. Although 8 out of 10 received SGAs, during an average 234 days of hospitalization, there was no significant change in any measure, and little change in medications.Conclusions: These preliminary r...

As a follow-up to our previous study of clozapine, medical records of a state psychiatric hospital were reviewed for patients who were prescribed an atypical antipsychotic. From that sample, demographic and clinical data were obtained for individuals with an initial score of 35 or greater on the Brief Psychiatric Rating Scale (BPRS), and at least two additional successive monthly BPRS ratings. A total of 100 patients met the criteria. Most received either olanzapine (46%) or risperidone (36%), with few administered quetiapine (11%) or clozapine (7%). Most also received adjunctive medications, including conventional antipsychotics, anticonvulsants/mood stabilizers, antidepressants, and antiparkinsonian agents. The number of patients whose BPRS total scores decreased by 20% or more from baseline was significantly greater for those who received olanzapine than those who received risperidone. However, there was no difference between the two antipsychotics in the number of patients who maintained that degree of improvement, in the average latency to achieve that decrease (1.67 and 1.47 months, respectively), or the average length of stay (LOS; 332 and 376 days, respectively). These results indicate a modest therapeutic advantage of olanzapine compared to risperidone, and a substantial degree of polypharmacy in the use of atypical antipsychotics. This uncontrolled "real-world" evaluation supports data from controlled clinical trials, showing that either risperidone or olanzapine would be a reasonable first choice in patients with treatment-resistant schizophrenia, with the decision based on the least adverse side effect profile and economic constraints. When compared to our previous clozapine study, we confirm a slight advantage for the effectiveness of clozapine in the treatment of this refractory population.

There has been an expanding role for the new generation atypical antipsychotic agents (clozapine, risperidone, olanzapine, and quetiapine) in elderly patients. Their efficacy in the treatment of psychoses associated with schizophrenia is now well established. But psychoses occur in other conditions. This paper will review the current research examining the use of the atypical agents in the treatment of psychoses in the elderly in three somewhat overlapping conditions: schizophrenia, dementia, and Parkinson's disease, as well as in the amelioration of a variety of movement disorders. In the elderly, any of the atypicals can be used to treat schizophrenia, although clozapine may be a second line agent because of its side effect profile. Risperidone may be the drug of choice for the treatment of psychoses and behavioral disturbances in dementia. Clozapine is a primary choice and quetiapine an alternative for the treatment of psychoses in Parkinson's disease; while clozapine and possibly risperidone may be preferred for the initial treatment of some movement disorders. The differential effectiveness of these agents across treatment indications may, in part, be related to their differing affinities at several neurotransmitter receptors. Examination of these relationships in large scale longitudinal studies may help in the development of effective tailored treatments for the elderly.

The Dual Diagnosis Capability in Mental Health Treatment (DDCMHT) Index was developed to assess the capability of mental health programs to provide substance abuse and co-occurring treatment services. The DDCMHT is an objective scale rated following a site visit that includes semi-structured interviews with staff at all levels, review of program documents and client charts, and ethnographic observation of the milieu and setting. Using data from 67 mental health programs across six states, this study found that the DDCMHT had excellent total score reliability, variable subscale reliability, high inter-rater reliability (n = 18), and moderate construct validity (n = 22). Results also suggest that many mental health programs are at a relatively low level of capability for the delivery of care to individuals with co-occurring disorders. Results from this important new benchmark measure, the DDCMHT, can be used with programs in implementation planning and with treatment systems, states, or national organizations to guide policy change.

This study describes the outcome of a token economy treatment applied to 2 distinct patient populations on the same unit of a state psychiatric hospital: individuals with a dual diagnosis of mental retardation and a DSM-IV Axis I diagnosis of either (a) a severe behavior disorder (BD) or (b) a serious and persistent psychiatric disorder (PD). Results showed that patients in the PD group were more likely to complete the treatment (17/20) than those in the BD group (17/31) who were more likely to be terminated from the program (14/31). Individuals who did not complete the program were distinguished early, within the first 3 weeks of treatment. These noncompleters received significantly more fines and earned significantly fewer tokens than those who completed the program. At an average of 2.7 years post-discharge, there was no difference in the proportion of PD (12/16) and BD completers (9/11) and BD noncompleters (3/7) remaining in the community. These data show that diverse populations of patients can be treated within the same token economy program, thereby improving cost effectiveness. Future research should be directed toward characterizing those patients (e.g., BD) less likely to succeed when they enter treatment, and determining if modifications in the program can improve that outcome.

1. A review of the medical records in a state psychiatric hospital was conducted to evaluate the clinical efficacy of the atypical antipsychotic, clozapine. 2. Using the Brief Psychiatric Rating Scale (BPRS), four groups of schizophrenic inpatients (n = 59) were operationally defined: Nonresponders (< 20% decrease from pre-drug baseline); Short-term Pharmacological Responders (20% decline, but not sustained); Long-term Pharmacological Responders (maintained a 20% decline) and Clinical Responders (maintained a 20% decline and achieved a BPRS < or = 36; the criterion of Kane et al. 1988). 3. There were 7 NRs, 13 STPRs, 21 LTPRs and 18 CRs 4. The STPR, LTPR and CR groups improved significantly within the first month of treatment and reached a 20% decrease in BPRS by 3 months. CRs required 5 months to attain a BPRS < or = 36. These criteria were reached at the same average doses (about 300-400 mg/day). 5. The proportion of CRs (30%) in this retrospective, naturalistic study, is remarkably close to the results of the definitive study by Kane et al. 1988. These results are also consistent with many of the controlled research studies of clozapine in hospitalized, treatment refractory psychiatric patients.

Clinical evidence indicates that phenothiazines, specifically chlorpromazine (CPZ), used extensively in the treatment of patients with mental and/or neurologic disorders produce an ileus characterized by pseudoobstruction with an extended barium transit time of eight to ten days. Postoperatively, these patients have a protracted ileus, lasting from ten to fourteen days. In our present study we investigated the mechanism of action by which phenothiazines block gastrointestinal tract function as well as the possible reversal of this effect by pharmacologic agents. Guinea pigs were injected intraperitoneally with CPZ at a dose of 30 mg/kg/day for five to seventeen days. This caused deleterious effects in the gastrointestinal tract, such as cessation of peristalsis of small intestine and colon, and marked distension of the cecum. In vitro pharmacologic studies were performed on the electrically stimulated longitudinal muscle-myenteric plexus of the guinea pigs. We found that phenothiazines interfered with the neuromuscular mechanism of the intestine, as exemplified by a lack of response to electrical current stimulation. The effect was protracted, lasting at least 24 hours. These effects were reversed by the administration of the anticholinesterase, physostigmine (PGM), provided the block was less than 80 per cent. The paralytic ileus produced was similar to that found in man.

Plasma and cerebrospinal fluid (CSF) levels of the major dopamine metabolite homovanillic acid (HVA) were measured in psychiatric patients after an average washout period of 19 days, and again after 4 weeks of pharmacological treatment. Absolute values of plasma HVA did not correlate with absolute values of CSF HVA either at baseline or after treatment. However, changes in plasma HVA were highly correlated with changes in CSF HVA. Further, while baseline levels of plasma and CSF HVA were not significantly correlated with baseline clinical measures, clinical improvement was associated with decreases in both plasma and CSF HVA. This reached statistical significance for the plasma HVA level/clinical response relationship.

Inhibitors of prostaglandin synthetase as well as prostaglandin receptor inhibitors block electrically induced contractions of the longitudinal muscle of the guinea pig ileum. This blockade is selectively reversed by some prostaglandins, particularly those of the E series. There is a very close parallel between the potency with which the synthetase inhibitors block transmission and inhibit the enzyme. That blockade is actually accompanied by inhibition of synthesis of PG was shown by inhibition of arachidonic acid contractions of the tissue by indomethacin. The inhibition of transmission by indomethacin involves block of acetylcholine release as shown by direct assay and by the fact that physostigmine can reverse the block. Physostigmine also reverses block of transmission by prostaglandin receptor inhibitors and by morphine but not that produced by chlorpromazine or papaverine. Other evidence for a presynaptic site of action for the synthetase and PG receptor inhibitors is indicated by lack of effect of blocking concentrations on response of the tissue to exogenous acetylcholine. That prostaglandin reverses block of transmission by a presynaptic effect was shown by lack of reversal of atropine and papaverine inhibition of electrically induced contractions; both of these drugs produce this effect directly on the smooth muscle. These results are compatible with the previous postulate that a prostaglandin system, comprised of prostaglandin, its synthesizing enzyme and its receptor, is directly involved with the release of acetylcholine in the ileum.

Norepinephrine block of electrically induced contractions of the guinea pig longitudinal muscle-myenteric plexus preparation reverses spontaneously. PGE1 or E2 fails to alter rate of reversal in the presence of ascorbic acid but increases the rate in its absence. Using spectrophotometry, it could be demonstrated that PGE1 or E2 significantly increases the rate of autoxidation of norepinephrine, thereby accounting for the pharmacological interaction observed.

The authors examined reports addressing the question of whether electroconvulsive therapy (ECT) is more effective in psychotic or nonpsychotic depressive disorders. Most ECT studies did not consider the issue directly, and those that did had varying methodologies and results. The authors then analyzed the data of 33 depressed patients to clarify the differential response to ECT in 13 psychotic and 20 nonpsychotic patients. The subjects were also examined as to type of electrode placement. ECT produced a greater reduction in Hamilton Depression Rating Scale scores in the psychotic depressives as compared to the nonpsychotics after an average of 9.2 treatments. The two patients who were nonresponders to ECT were both nonpsychotic.

The authors present new data on the results of the pretreatment Dexamethasone Suppression Test (DST) in 164 drug-free inpatients, as well as on the effects of age on postdex-amethasone cortisol values. Nonsuppression rates were 18% in schizophrenic patients ( n = 44), versus 46% in patients with a major depression ( n = 56). In addition, a significant correlation was found between age and the 4:00 PM postdexamethasone cortisol value among the depressed patients ( r = 0.33). The authors then applied a metaanalysis to summarize 25 other studies that have addressed the schizophrenia/major depression dichotomy as it relates to the DST outcome. Nonsuppression rates were consistently different in schizophrenic patients (19%) when compared to patients with a major depression (51 %) or normal controls (7%). These differences were highly significant as measured by the Mantel-Haenszel chi-square statistic. A metaanalysis applied to a series of correlations obtained from 14 other studies reporting an agei'postdexamethasone cortisol relationship in affective patients indicated a modest, but significant correlation ( r = 0.24) in a total of 1284 patients ( p −8 ).

A study was made of the effect of morphine on electrical activity within single ganglia of Auerbach's plexus of guinea pig longitudinal muscle-myenteric plexus as monitored by means of external electrodes. Morphine produces a concentration dependent block of single spike activity. This effect is competitively antagonized by naloxone. The ED50 for morphine effect is about 7 X 10(-7) M. Naloxone and dextrorphan have no effect on electrical activity. Acetylcholine in the concentration range of 10(-7)--10(-5) M augments electrical activity of ganglia. Morphine has little if any effect on the enhanced stimulation produced by acetylcholine thus indicating that the drug does not act directly upon the ganglion. Our results suggest that a specific opiate receptor is present on the preganglionic nerve terminals and that morphine and other opiates block ganglionic transmission by inhibiting the release of preganglionic acetylcholine.

Injection of a large dose of morphine into a guinea pig results in a block of electrically-induced contractions of the ileum in vitro . A similar dose is almost ineffective in guinea pigs given morphine chronically. The time course for development of this tolerance has been determined in guinea pigs injected twice daily with morphine 100 mg/kg and challenged on various days with 750 mg/kg of the drug. Animals similarly injected but not challenged served as controls. The inhibitory effect of the challenging dose on electrical stimulation of longitudinal muscle decreased with successive days of morphine administration; by the 10th day there was almost complete tolerance to the challenging dose. Sensitivity of the tissues of chronically morphinized unchallenged controls towards acetylcholine, serotonin, histamine and norepinephrine was essentially the same as that of naive animals. The potency of morphine in vitro in blocking electrical stimulation was also unchanged by chronic morphine administration in the above manner. Thus tolerance to injected morphine cannot be explained by reduced affinity of the drug for the opiate receptor. Tissues of chronically morphinized animals gave a contracture with naloxone, the extent of the contracture increasing with time of drug administration. This naloxone effect is attributed to displacement of morphine from a new opiate receptor site induced during morphine administration. It is suggested that this new receptor is involved in tolerance to injected morphine as well as some aspects of the withdrawal syndrome.

High potency neuroleptics have been advocated for acute mania because their side effect profile may allow for a more rapid dose escalation and symptom resolution. Low potency neuroleptics have also been advocated because their sedative properties might better calm the acutely agitated manic patient. The authors tested these hypotheses using a double-blind design comparing thiothixene with chlorpromazine in 29 manic patients on a standard dose of lithium. They found that thiothixene and chlorpromazine produced identical rates and degree of improvement, that side effect profiles differed for each drug but did not affect overall clinical response, and that most patients had a good response on much lower than expected doses. The implications for less aggressive use of neuroleptics to treat mania are discussed.

The authors studied 36 acutely psychotic inpatients who were diagnosed as having either a schizophrenic (N = 30) or other psychotic (N = 6) disorder. After a washout phase averaging 18 days, all patients were placed on trifluoperazine 5 mg orally twice a day. Plasma levels of trifluoperazine were obtained on days 11 and 15 of treatment and then compared with clinical response. After 2 weeks of treatment an inverted U-shaped relationship was found between change scores on the Brief Psychiatric Rating Scale and trifluoperazine plasma levels.