Functional and work disability and treatment received by patients with major depressive disorder

This study is one part of a collaborative depression research project, the Vantaa Depression Study (VDS), involving the Department of Mental and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry of the Peijas Medical Care District (PMCD), Vantaa, Finland. The VDS includes two parts, a record-based study consisting of 803 patients, and a prospective, naturalistic cohort study of 269 patients. Both studies include secondary-level care psychiatric out- and inpatients with a new episode of major depressive disorder (MDD). Data for the record-based part of the study came from a computerised patient database incorporating all outpatient visits as well as treatment periods at the inpatient unit. We included all patients aged 20 to 59 years old who had been assigned a clinical diagnosis of depressive episode or recurrent depressive disorder according to the International Classification of Diseases, 10th edition (ICD-10) criteria and who had at least one outpatient visit or day as an inpatient in the PMCD during the study period January 1, 1996, to December 31, 1996. All those with an earlier diagnosis of schizophrenia, other non-affective psychosis, or bipolar disorder were excluded. Patients treated in the somatic departments of Peijas Hospital and those who had consulted but not received treatment from the psychiatric consultation services were excluded. The study sample comprised 290 male and 513 female patients. All their psychiatric records were reviewed and each patient completed a structured form with 57 items. The treatment provided was reviewed up to the end of the depression episode or to the end of 1997. Most (84%) of the patients received antidepressants, including a minority (11%) on treatment with clearly subtherapeutic low doses. During the treatment period the depressed patients investigated averaged only a few visits to psychiatrists (median two visits), but more to other health professionals (median seven). One-fifth of both genders were inpatients, with a mean of nearly two inpatient treatment periods during the overall treatment period investigated. The median length of a hospital stay was 2 weeks. Use of antidepressants was quite conservative: The first antidepressant had been switched to another compound in only about one-fifth (22%) of patients, and only two patients had received up to five antidepressant trials. Only 7% of those prescribed any antidepressant received two antidepressants simultaneously. None of the patients was prescribed any other augmentation medication. Refusing antidepressant treatment was the most common explanation for receiving no antidepressants. During the treatment period, 19% of those not already receiving a disability pension were granted one due to psychiatric illness. These patients were nearly nine years older than those not pensioned. They were also more severely ill, made significantly more visits to professionals and received significantly more concomitant medications (hypnotics, anxiolytics, and neuroleptics) than did those receiving no pension. In the prospective part of the VDS, 806 adult patients were screened (aged 20-59 years) in the PMCD for a possible new episode of DSM-IV MDD. Of these, 542 patients were interviewed face-to-face with the WHO Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Version 2.0. Exclusion criteria were the same as in the record-based part of the VDS. Of these, 542 269 patients fulfiled the criteria of DSM-IV MDE. This study investigated factors associated with patients' functional disability, social adjustment, and work disability (being on sick-leave or being granted a disability pension). In the beginning of the treatment the most important single factor associated with overall social and functional disability was found to be severity of depression, but older age and personality disorders also significantly contributed. Total duration and severity of depression, phobic disorders, alcoholism, and personality disorders all independently contributed to poor social adjustment. Of those who were employed, almost half (43%) were on sick-leave. Besides severity and number of episodes of depression, female gender and age over 50 years strongly and independently predicted being on sick-leave. Factors influencing social and occupational disability and social adjustment among patients with MDD were studied prospectively during an 18-month follow-up period. Patients' functional disability and social adjustment were alleviated during the follow-up concurrently with recovery from depression. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support also had a significant influence. During the 18-month follow-up period, of the 269, 13 (5%) patients switched to bipolar disorder, and 58 (20%) dropped out. Of the 198, 186 (94%) patients were at baseline not pensioned, and they were investigated. Of them, 21 were granted a disability pension during the follow-up. Those who received a pension were significantly older, more seldom had vocational education, and were more often on sick-leave than those not pensioned, but did not differ with regard to any other sociodemographic or clinical factors. Patients with MDD received mostly adequate antidepressant treatment, but problems existed in treatment intensity and monitoring. It is challenging to find those at greatest risk for disability and to provide them adequate and efficacious treatment. This includes great challenges to the whole society to provide sufficient resources.

Assessment of neuroleptic-induced movement disorders in a naturalistic schizophrenia population

The prevalence and assessment of neuroleptic-induced movement disorders (NIMDs) in a naturalistic schizophrenia population that uses conventional neuroleptics were studied. We recruited 99 chronic schizophrenic institutionalized adult patients from a state nursing home in central Estonia. The total prevalence of NIMDs according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) was 61.6%, and 22.2% had more than one NIMD. We explored the reliability and validity of different instruments for measuring these disorders. First, we compared DSM-IV with the established observer rating scales of Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS) (for neuroleptic-induced parkinsonism, NIP) and Abnormal Involuntary Movement Scale (AIMS) (for tardive dyskinesia), all three of which have been used for diagnosing NIMD. We found a good overlap of cases for neuroleptic-induced akathisia (NIA) and tardive dyskinesia (TD) but somewhat poorer overlap for NIP, for which we suggest raising the commonly used threshold value of 0.3 to 0.65. Second, we compared the established observer rating scales with an objective motor measurement, namely controlled rest lower limb activity measured by actometry. Actometry supported the validity of BARS and SAS, but it could not be used alone in this naturalistic population with several co-existing NIMDs. It could not differentiate the disorders from each other. Quantitative actometry may be useful in measuring changes in NIA and NIP severity, in situations where the diagnosis has been made using another method. Third, after the relative failure of quantitative actometry to show diagnostic power in a naturalistic population, we explored descriptive ways of analysing actometric data, and demonstrated diagnostic power pooled NIA and pseudoakathisia (PsA) in our population. A subjective question concerning movement problems was able to discriminate NIA patients from all other subjects. Answers to this question were not selective for other NIMDs. Chronic schizophrenia populations are common worldwide, NIMD affected two-thirds of our study population. Prevention, diagnosis and treatment of NIMDs warrant more attention, especially in countries where typical antipsychotics are frequently used. Our study supported the validity and reliability of DSM-IV diagnostic criteria for NIMD in comparison with established rating scales and actometry. SAS can be used with minor modifications for screening purposes. Controlled rest lower limb actometry was not diagnostically specific in our naturalistic population with several co-morbid NIMDs, but it may be sensitive in measuring changes in NIMDs.

Potentially inappropriate prescribing among older people in the United Kingdom

Background: Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ≥70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators.

Methods: A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged ≥ 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (≥4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison.

Results: Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70–74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics.

Conclusions: PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.

D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.

It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking alpha1b-adrenergic receptors [alpha1b-adrenergic receptor knock-outs (alpha1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg d-amphetamine in alpha1bAR-KO mice [-84 and -74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of d-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of alpha1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in alpha1bAR-KO than in WT littermates (-28%; p < 0.001). In rats however, prazosin, an alpha1-adrenergic antagonist, decreases d-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local d-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release. Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of alpha1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that alpha1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-alpha1-adrenergic properties.

Outpatient treatment of acute psychotic episode with neuroleptic infusions: a retrospective study.

In this retrospective pragmatic study, we define the necessary conditions that allow outpatient low dose intravenous neuroleptization, when hospitalization should otherwise be required. Intravenous neuroleptization is infrequently used in the outpatient treatment of acute psychotic decompensation. Rapid tranquilization with high dosage neuroleptics is controversial, and has a high risk of side effects. The indications for and potential advantages of this method in the perspective of a long-term ambulatory treatment are discussed by comparing a group of outpatients treated with infusions to a group of hospitalized patients. The method offers a satisfactory alternative to hospitalization for subjects who are not in imminent danger (current GAF rating between 20 and 40) and whose normal functioning is good (past year GAF rating = 70). Previous repeated hospitalizations favor the choice of hospitalization over infusion. Its potential advantages are the rapid evolution of the condition, with controlled regression but without psychosocial withdrawal, and an improvement in the patient's attitude towards treatment.

Vue intérieure de la médication psychiatrique : l’expérience des personnes ayant cheminé avec la GAM

Cette recherche aborde la médication psychiatrique à partir du point de vue des usagers. Des entrevues en profondeur ont été réalisées auprès de dix personnes utilisatrices en provenance d’une ressource communautaire et alternative en santé mentale. Les répondants éprouvent ou ont éprouvé des problèmes importants de santé mentale. La majorité des usagers de notre échantillon consomme des neuroleptiques. Les participants sélectionnés ont cheminé avec l’approche de la gestion autonome de la médication en santé mentale (GAM). La GAM constitue un terrain fertile, car l’approche favorise la réflexion critique, la diversité de pratiques autour de la médication psychotrope. Un état des connaissances portant sur l’expérience subjective de la médication est présenté. Les effets de la médication sur les personnes et leur contexte de vie ainsi que les aspects symboliques ont été analysés. Parmi les effets majeurs de la médication, on compte : l’effet de « gel », la grande fatigue, les difficultés d’attribution, le désir d’arrêt et les effets paradoxaux. La médication peut avoir des effets positifs ou négatifs sur l’entourage, le travail, les études ou autres implications sociales. Le rapport des usagers relatif à la médication a évolué vers un usage planifié, modulé et moindre. À cet effet, les dix usagers sont passés d’une phase de « novice » à une « d’expert ». Les résultats de cette recherche indiquent que la notion d’observance au traitement doit être revisitée et la notion d’efficacité élargie. Cette étude qualitative démontre que les versants « intérieurs » de la médication, l’expérience subjective et l’intersubjectif apportent une perspective plutôt rare, mais riche, du médicament en tant qu’objet social.

Eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del alzhéimer: revisión sistemática

Introducción: El Alzhéimer tiene una prevalencia de 1,6% en las personas mayores de 65 años. Se caracteriza por la pérdida de memoria y otras funciones cognoscitivas, pero más del 70% de los afectados presentan síntomas no cognitivos entre los que se encuentran alteraciones del afecto, comportamiento y psicosis. Estos síntomas están asociados a mayores tasas de institucionalización, morbilidad y mortalidad. Métodos: Revisión sistemática de la literatura de artículos que proporcionaron información sobre la eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del Alzhéimer. Resultados: La búsqueda inicial arrojó un total de 495 resultados, 64 artículos fueron preseleccionados y 7 se incluyeron en la revisión; éstos se clasificaron como nivel de evidencia Ib; citalopram mostró ser más eficaz que el placebo y similar a antipsicóticos para síntomas comportamentales y psicóticos asociados al Alzhéimer con un perfil de efectos adversos más tolerable; sertralina no mostró eficacia en depresión y sí una mayor incidencia de efectos adversos con respecto al placebo. Discusión: Se obtuvieron resultados favorables en síntomas comportamentales y psicóticos pero no en afectivos. Las diferencias metodológicas de los estudios le dan complejidad a la interpretación de los resultados. Conclusión: La evidencia sugiere que el tratamiento con citalopram es eficaz en síntomas comportamentales y psicóticos asociados al Alzhéimer; para el tratamiento de la depresión asociado a esta demencia aún no existe un antidepresivo que pueda considerarse de elección.

A fortaleza assediada

O conceito de Psicanálise Aplicada foi fabricado por Lacan para dar nome A prática psicanalítica nas modernas Instituições de Saúde Mental. Esta comunicação apresenta o caso de um esquizofrénico que ocultou aos psiquiatras o conteúdo do seu delírio, até que foi tratado por um analista. Não usou o saber científico (neurolépticos, etc.), mas escutando o duplo sentido dos seus ditos e lendo os seus escritos sob transferência:

Um programa de saúde mental: A experiência do Projeto UNI de Botucatu

The aim of this paper was to assess the Projeto UNI (Kellogg Foundation) in one of the Mental Health Centers (ARE) of Botucatu, SP, Brazil. We analysed 20% of the charts and the number of patients seen by psychiatrists and other mental health professionals before and after. Our results showed that: 1) the service users were mainly of neurotic patients (anxious, dysthymiacs, ICD-9 V code), followed by psychotics (schizophrenics, affectives) and organics (epileptics, mental deficients, demented patients); 2) there were more treatment options after the Projeto UNI implementation and over 2,495 group consultations were made in one year (as opposed to 90 in the year prior the project); 3) medical and nurse students are evaluating the program favourably; 4) there is a clear necessity of reassessing and changing some prescription practices: 43% of the patients were taking drug associations, there was an excessive use of benzodiazepines (54%) and low use of mood stabilizers (5%). There is also a need for more availability of depot neuroleptics, other antidepressants and better quality psychotropic drugs, and 5) there is a necessity of improving quality and quantity of charts information.

Associações neuroleptoanalgésicas em equinos

The equine anesthesia is proven to be a high risk procedure, for both patient and anesthetist, compared to other animal species. In these conditions, a good anesthetic protocol that can deliver sedation, making access and manipulation easier, analgesia fair enough to realize cirurgical procedures, and minimal physiologic changes would be ideal. Since there aren’t any drugs suporting all these qualities, the Neuroleptoanalgesic Associations show themselves as a valuable technique to provide anesthetic quality and safety, possibly diminishing our drug of choice’s doses, therefore offering less fisiological changes and easier monetary access in some cases. This paper objective was to list all these associations found in literature, evaluating their advantages and practical applications

Untersuchung neuer hochwirksamer neuroprotektiver Antioxidantien in experimentellen Modellen der Parkinsonschen Krankheit

Bei der Parkinsonschen Krankheit kommt es zu einer selektiven Degeneration der dopaminergen Neurone in der Substantia nigra pars compacta. Die Rolle des oxidativen Stresses in der Pathogenese dieser Erkrankung konnte an post mortem Untersuchungen der Parkinson-Patienten, wie auch an zahlreichen in vitro und in vivo Modellen bestätigt werden. Die Anwendung von Antioxidantien wurde als therapeutische Strategie der Parkinsonschen Krankheit vorgeschlagen. In dieser Hinsicht wurden bereits antioxidative Substanzen in klinischen Studien evaluiert. Klinische Studien mit Antioxidantien haben jedoch bislang nur wenig überzeugende Ergebnisse erbracht, mit Ausnahme des Einsatzes des Ubichinons (Coenzym Q). Eine kritische Analyse der klinischen Studien lässt zusammenfassen, dass auf Seiten der verwendeten Antioxidantien noch massiver Optimierungsbedarf besteht. Für einen erfolgreichen therapeutischen Einsatz von Antioxidantien bei dieser Krankheit sind folgende Eigenschaften der Substanzen von höchster Bedeutung: i) maximale neuroprotektive Aktivität bei geringen Dosen; ii) geringe Nebenwirkungen; iii) eine hohe Blut-Hirn-Schrankengängigkeit.In dieser Arbeit wurde das neuroprotektive Potential von drei Bisarylimin-basierten antioxidativen Strukturen (Phenothiazin, Iminostilben und Phenoxazin) in in vitro und in vivo Parkinson-Modellsystemen evaluiert. Beide experimentellen Modelle basieren auf der Wirkung der mitochondrialen Komplex I Inhibitoren 1-Methyl-4-Phenylpyridin (MPP+) und Rotenon, welche pathophysiologische Charakteristika der Parkinsonschen Krankheit reproduzieren. Unsere in vitro Untersuchungen an primären Neuronen des Mittelhirns und der klonalen SH-SY5Y-Neuroblastomazelllinie konnten zeigen, dass die Komplex I Inhibition krankheitsspezifische zelluläre Merkmale induziert, wie die Abnahme der antioxidativen Verteidigungskapazität und Verlust des mitochondrialen Membranpotentials. Zusätzlich kommt es in primären Neuronen des Mittelhirns zur selektiven Degeneration dopaminerger Neurone, welche in der Parkinsonschen Erkrankung besonders betroffen sind. Ko-Inkubation der in vitro Modelle mit Phenothiazin, Iminostilben und Phenoxazin in niedrigen Konzentrationen (50 nM) halten die pathologischen Prozesse fast vollständig auf. In vivo Untersuchungen am MPP+- und Rotenon-basierten Caenorhabditis elegans (C. elegans) Modell bestätigen das neuroprotektive Potential der Bisarylimine. Hierfür wurde eine transgene C. elegans Linie mithilfe einer dopaminerg spezifischen DsRed2- (Variante des rot fluoreszierenden Proteins von Discosoma sp.)-Expression und pan-neuronaler CFP- (cyan fluoreszierendes Protein)-Expression zur Visualisierung der dopaminergen Neuronenpopulation in Kontrast zum Gesamtnervensystem erstellt. Behandlung des C. elegans mit MPP+ und Rotenon im larvalen und adulten Stadium führt zu einer selektiven Degeneration dopaminerger Neurone, sowie zum Entwicklungsarrest der larvalen Population. Die dopaminerge Neurodegeneration, wie auch weitere phänotypische Merkmale des C. elegans Modells, können durch Phenothiazin, Iminostilben und Phenoxazin in niedrigen Konzentrationen (500 nM) komplett verhindert werden. Ein systemischer Vergleich aromatischer Bisarylimine mit bekannten, gut charakterisierten Antioxidantien, wie α-Tocopherol (Vitamin E), Epigallocatechingallat und β-Catechin, zeigt, dass effektive Konzentrationen für Phenothiazin, Iminostilben und Phenoxazin um Zehnerpotenzen niedriger liegen im Vergleich zu natürlichen Antioxidantien. Der Wirkungsmechanismus der Bisarylimine konnte in biochemischen und in vitro Analysen, sowie in Verhaltensuntersuchungen an C. elegans von der Wirkungsweise strukturell ähnlicher, neuroleptisch wirkender Phenothiazin-Derivate differenziert werden. Die Analyse des dopaminerg-gesteuerten Verhaltens (Beweglichkeit) in C. elegans konnte verdeutlichen, dass antioxidative und Dopaminrezeptor-bindende Eigenschaften der Bisaryliminstrukturen sich gegenseitig ausschließen. Diese qualitativen Merkmale unterscheiden Bisarylimine fundamental von klinisch angewandten Neuroleptika (Phenothiazin-Derivate), welche als Dopaminrezeptor-Antagonisten zur Behandlung psychischer Erkrankungen klinisch eingesetzt werden.Aromatische Bisarylimine (Phenothiazin, Iminostilben und Phenoxazin) besitzen günstige strukturelle Eigenschaften zur antioxidativ-basierter Neuroprotektion. Durch die Anwesenheit der antioxidativ wirkenden, nicht-substituierten Iminogruppe unterscheiden sich Bisarylimine grundlegend von neuroleptisch-wirkenden Phenothiazin-Derivaten. Wichtige strukturelle Voraussetzungen eines erfolgreichen antioxidativen Neuropharmakons, wie eine hohe Radikalisierbarkeit, die stabile Radikalform und der lipophile Charakter des aromatischen Ringsystems, werden in der Bisaryliminstruktur erfüllt. Antioxidative Bisarylimine könnten in der Therapie der Parkinsonschen Krankheit als eine effektive neuroprotektiv-therapeutische Strategie weiter entwickelt werden.

Role of cholinesterase inhibitors in Parkinson's disease and dementia with Lewy bodies

This article reviews the cholinergic changes in Parkinson's disease and dementia (PDD) and dementia with Lewy bodies (DLB), their potential clinical implications, and the available evidence for cholinesterase inhibitors in the treatment of PDD and DLB. Marked neuronal loss of cholinergic nuclei, reduced cholinergic markers in the neocortex, hippocampus, and selected thalamic nuclei, and receptor changes have been reported. One large and 2 small placebo-controlled trials and nearly 20 open-label studies suggest that cholinesterase inhibitors have a positive effect on cognition, psychiatric symptoms, and global function in patients with DLB and PDD. The treatment is well tolerated in most patients without any apparent worsening of extrapyramidal motor features. Given the high risk of severe sensitivity reactions and increased risk of cerebrovascular incidents during treatment with neuroleptics, more clinical trials of cholinesterase inhibitors are encouraged to establish their precise role in DLB and PDD.

Lithium for schizophrenia revisited: A systematic review and meta-analysis of randomized controlled trials

Background: Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia. Data sources and study selection: Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early. Results: The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p = .07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone. Conclusion: Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.

Assessing cost-effectiveness of drug interventions for schizophrenia

Objective: To assess from a health sector perspective the incremental cost-effectiveness of eight drug treatment scenarios for established schizophrenia. Method: Using a standardized methodology, costs and outcomes are modelled over the lifetime of prevalent cases of schizophrenia in Australia in 2000. A two-stage approach to assessment of health benefit is used. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted, using best available evidence. The robustness of results is tested using probabilistic uncertainty analysis. The second stage involves application of 'second filter' criteria (equity, strength of evidence, feasibility and acceptability) to allow broader concepts of benefit to be considered. Results: Replacing oral typicals with risperidone or olanzapine has an incremental cost-effectiveness ratio (ICER) of A$48 000 and A$92 000/DALY respectively. Switching from low-dose typicals to risperidone has an ICER of A$80 000. Giving risperidone to people experiencing side-effects on typicals is more cost-effective at A$20 000. Giving clozapine to people taking typicals, with the worst course of the disorder and either little or clear deterioration, is cost-effective at A$42 000 or A$23 000/DALY respectively. The least cost-effective intervention is to replace risperidone with olanzapine at A$160 000/DALY. Conclusions: Based on an A$50 000/DALY threshold, low-dose typical neuroleptics are indicated as the treatment of choice for established schizophrenia, with risperidone being reserved for those experiencing moderate to severe side-effects on typicals. The more expensive olanzapine should only be prescribed when risperidone is not clinically indicated. The high cost of risperidone and olanzapine relative to modest health gains underlie this conclusion. Earlier introduction of clozapine however, would be cost-effective. This work is limited by weaknesses in trials (lack of long-term efficacy data, quality of life and consumer satisfaction evidence) and the translation of effect size into a DALY change. Some stakeholders, including SANE Australia, argue the modest health gains reported in the literature do not adequately reflect perceptions by patients, clinicians and carers, of improved quality of life with these atypicals.

An investigation into the pharmacology of tics and tic-like movements

The study of tic-like movements in mice has demonstrated close parallels both in characteristics and in pharmacology with the tics which occur in TS. Head-shakes and/or other tic-like behaviours occurring spontaneously or induced by the selective 5-HT2/1C agonist DOI, alpha-melanocyte stimulating hormone, adrenocorticotrophic hormone (1-39), thyrotropin releasing hormone, or RX336-M were blocked when tested with neuroleptics such as haloperidol and/or the alpha-2 adrenoceptor agonist clonidine. The selective dopamine D1 antagonists SCH23390 and SCH39166 dose-dependently blocked spontaneous and DOI head-shakes but the selective dopamine D2 antagonists sulpiride and raclopride were ineffective. The 5-HT1A receptor agonists 8-OH-DPAT, ipsapirone, gepirone, MDL 73005EF and buspirone (i.p) dose-dependently blocked DOI head-shakes, pindolol blocked the inhibitory effect of 8-OH-DPAT on DOI head-shakes. Parachlorophenylalanine blocked the inhibitory effect of 8-OH-DPAT and buspirone, suggesting that the 5-HT1A receptor involved is located presynaptically. The alpha-2 adrenoceptor antagonists yohimbine, idazoxan, 1-PP and RX811059 prevented the inhibitory effect of 8-OH-DPAT on DOI head-shakes suggesting that this 5-HT1A - 5-HT2 receptor interaction is under the modulatory control of adrenoceptors. Because kynurenine has previously been found to potentiate head-shaking, plasma kynurenine concentrations were measured in seven TS patients and were significantly higher than controls, but neopterin and biopterin were unchanged. The relationship between tic-like movements in rodents and their implications for understanding the aetiology and treatment of TS is discussed.