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1.
Pain ; 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35472065

RESUMO

ABSTRACT: Pain and related consequences could contribute to comorbid illness and premature mortality in homeless and precariously housed persons. We analyzed longitudinal data from an ongoing naturalistic prospective study of a community-based sample (n = 370) to characterize risk factors and consequences of bodily pain. The aims were to describe bodily pain and associations with symptoms and psychosocial function, investigate factors that may increase or ameliorate pain, and examine the consequences of pain for symptoms, functioning, and all-cause mortality. Bodily pain severity and impact were rated with the 36-item Short Form Health Survey Bodily Pain Scale monthly over 5 years. Mixed-effects linear regression models estimated the effects of time-invariant and time-varying risk factors for pain, verified by reverse causality and multiple imputation analysis. Regression models estimated the associations between overall person-mean pain severity and subsequent functioning and suicidal ideation, and Cox proportional hazard models assessed association with all-cause mortality. Bodily pain of at least moderate severity persisted (>3 months) in 64% of participants, exceeding rates expected in the general population. Greater pain severity was associated with depressive symptom severity and month-to-month opioid use, overlaid on enduring risk associated with age, arthritis, and posttraumatic stress disorder. The frequency of prescribed and nonprescribed opioid use had nonlinear relationships with pain: intermittent use was associated with severe pain, without reverse association or change with the overdose epidemic. Greater longitudinal mean pain severity was associated with premature mortality, poorer functioning, and suicidal ideation. Considering the relationships between pain, intermittent opioid use, and depressive symptoms could improve health care for precariously housed patients.

2.
PLoS One ; 17(4): e0267808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35486616

RESUMO

AIM: Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients. METHODS: MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. RESULTS: 33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations. CONCLUSIONS: While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Antipsicóticos/efeitos adversos , Estudos de Coortes , Preparações de Ação Retardada , Humanos , Palmitato de Paliperidona , Transtornos Psicóticos/tratamento farmacológico , Risperidona
3.
Front Pharmacol ; 13: 765905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242029

RESUMO

The second-generation antipsychotic drugs are widely used in the field of psychiatry, for an expanding number of different conditions. While their clinical efficacy remains indispensable, many of the drugs can cause severe metabolic side-effects, resulting in an increased risk of developing cardiometabolic disorders. The physiological basis of these side-effects remains an ongoing area of investigation. In the present study, we examined the potential role of peripheral catecholamines in antipsychotic-induced glucose intolerance. Adult female rats were acutely treated with either the first-generation antipsychotic drug haloperidol (0.1, 0.5 or 1 mg/kg) or the second-generation drugs risperidone (0.25, 1.0 or 2.5 mg/kg), olanzapine (1.5, 7.5 or 15 mg/kg) or clozapine (2, 10 or 20 mg/kg) or vehicle. Fasting glucose levels were measured and then animals were subjected to the intraperitoneal glucose tolerance test. Levels of peripheral norepinephrine, epinephrine and dopamine were concurrently measured in the same animals 75, 105 and 135 min after drug treatment. All antipsychotics caused glucose intolerance, with strongest effects by clozapine > olanzapine > risperidone > haloperidol. Plasma catecholamines were also increased by drug treatment, with greatest effects for norepinephrine and epinephrine caused by clozapine > risperidone > olanzapine > haloperidol. Importantly, there were strong and statistically significant associations between norepinephrine/epinephrine levels and glucose intolerance for all drugs. These findings confirm that increases in peripheral catecholamines co-occur in animals that exhibit antipsychotic-induced glucose intolerance, and these effects are strongly associated with each other, providing further evidence for elevated catecholamines as a substrate for antipsychotic metabolic side-effects.

5.
Subst Use Misuse ; 56(13): 1951-1961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34338612

RESUMO

BACKGROUND: opioid use, which includes both prescribed and non-prescribed drugs, is relatively common amongst marginalized populations. Past research has shown that among those who use non-prescribed or diverted opioids recreationally, many were first exposed to the drug as prescribed pain medication. Objective: to better understand the relationship between pain and opioid use in tenants of precarious housing. Methods: in the present study, 440 individuals from a cohort living in homeless or precariously housed conditions in a neighborhood with high rates of poverty and drug use were interviewed for their bodily pain and opioid use. We examined the relationship between bodily pain levels, assessed using the Maudsley Addiction Profile questionnaire, and prescribed, non-prescribed and combined self-reported opioid use in the prior 28 days assessed using the Timeline Followback and Doctor-Prescribed Medication Timeline Followback questionnaires. Results: Analysis of the results indicated that sex (female), age (younger) and early exposure to opioids (≤ age 18) predicted current opioid use, but there was no association between current bodily pain levels and opioid use. Conclusions: these unexpected findings indicate the complex nature of the relationship between pain and opioid use in this population.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Adolescente , Analgésicos Opioides/uso terapêutico , Feminino , Habitação , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico , Dor/epidemiologia , Prescrições
6.
Front Psychol ; 12: 571423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276459

RESUMO

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, "real-world" consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to "real-world" behaviors.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34263540

RESUMO

AIM: Long-acting injectable antipsychotic drugs (LAIs) are often used as an alternative to oral antipsychotics (OAPs) in individuals with psychosis who demonstrate poor medication adherence. Previous meta-analyses have found mixed results on the efficacy of LAIs, compared to OAPs, in patients with psychotic disorders. The objective of this meta-analysis was to compare the effectiveness of using LAIs versus OAPs in the early stages of psychosis. METHODS: Major electronic databases were used to search for any studies examining the comparative effectiveness (i.e., relapse, adherence, hospitalization, and all-cause discontinuation) of any LAIs versus OAPs in early stages of psychosis. Studies published up to 6 June, 2019 were included and no language restriction was applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. Data were analysed using a random-effects model. RESULTS: Fifteen studies (n = 10 584) were included, of which were 7 RCTs, 7 observational studies, and 1 post-hoc analysis. We found that LAIs provided advantages over OAPs in terms of relapse rates. No significant differences were found between LAI and OAP groups in terms of all-cause discontinuation, hospitalization, and adherence rates. However, considering only RCTs revealed advantages of LAIs over OAPs in terms of hospitalization rates. CONCLUSIONS: LAIs may provide benefits over OAPs with respect to reducing relapse and hospitalization rates in early psychosis patients. There is a need for larger and better-designed studies comparing OAPs and LAIs specifically in early psychosis patients.

8.
Pharmacy (Basel) ; 9(3)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34287361

RESUMO

Second-generation antipsychotic medications are used to treat schizophrenia and a range of other psychotic disorders, although adverse effects, including cardiovascular and metabolic abnormalities and extrapyramidal symptoms, are often inevitable. Studies have shown that exercise, as an adjunct therapy, can be effective in reducing the core symptoms of schizophrenia as well as ameliorating intrinsic and antipsychotic-induced cardiometabolic abnormalities. However, it is noteworthy that exercise may need to be implemented with caution in some individuals receiving certain antipsychotic treatment regimens. We report here two cases of exercise-associated worsening of extrapyramidal symptoms in two individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication over the course of a 12-week exercise program. This worsening of extrapyramidal symptoms can be attributed to an increase in blood flow to the site of injection during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 receptor blockade. When monitoring drug therapy for patients receiving long-acting injectable antipsychotic medications, pharmacists and other healthcare professionals need to consider exercise as a contributing factor for the emergence of extrapyramidal symptoms.

9.
NPJ Schizophr ; 7(1): 29, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035313

RESUMO

Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D2 receptor (D2R) partial agonists and D2R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D2R partial agonists with D2R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D2R partial agonist, and was not significantly different from pooled D2R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D2R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D2R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole's efficacy did not differ substantially from D2R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D2R partial agonists with D2R antagonists in early stages of schizophrenia.

10.
Psychoneuroendocrinology ; 129: 105257, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023734

RESUMO

Clozapine is a second generation antipsychotic drug that has proven to be helpful in the management of patients with psychotic disorders that are resistant to other medications. Unfortunately, the majority of patients treated with clozapine develop metabolic dysregulation, including weight gain and insulin resistance. There are few treatments available to effectively counter these side-effects. The goal of the present study was to use an established animal model to better understand the nature of these metabolic side-effects and determine whether existing drugs could be used to alleviate metabolic changes. Adult female rats were treated with a range of doses of clozapine (2, 10 and 20 mg/kg) and subjected to the hyperinsulinemic-euglycemic clamp, to measure whole-body insulin resistance. Clozapine dose-dependently decreased the glucose infusion rate, reflecting pronounced insulin resistance. To reverse the insulin resistance, rats were co-treated with the ganglionic blocker mecamylamine (0.1, 1.0 and 5.0 mg/kg) which dose-dependently reversed the effects of 10 mg/kg clozapine. A 1.0 mg/kg dose of mecamylamine independently reversed the large increase in peripheral epinephrine caused by treatment with clozapine. To study the influence of specific adrenoceptors, rats were treated with multiple doses of α1 (prazosin), α2 (idazoxan), ß1 (atenolol) and ß2 (butoxamine) adrenoceptor antagonists after the onset of clozapine-induced insulin resistance. Both beta blockers were effective in attenuating the effects of clozapine, while idazoxan had a smaller effect; no change was seen with prazosin. The current results indicate that peripheral catecholamines may play a role in clozapine's metabolic effects and be a target for future treatments.


Assuntos
Antagonistas Adrenérgicos , Clozapina , Bloqueadores Ganglionares , Resistência à Insulina , Antagonistas Adrenérgicos/farmacologia , Animais , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Clozapina/efeitos adversos , Clozapina/farmacologia , Interações Medicamentosas , Feminino , Bloqueadores Ganglionares/farmacologia , Resistência à Insulina/fisiologia , Mecamilamina/farmacologia , Ratos
11.
Front Endocrinol (Lausanne) ; 12: 609240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716966

RESUMO

The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates of extrapyramidal symptoms and hyperprolactinemia compared to other antipsychotic drugs. However, clozapine tends to be underutilized in clinical practice due to a number of disabling and serious side-effects. These are characterized by a constellation of metabolic side-effects which include dysregulation of glucose, insulin, plasma lipids and body fat. Many patients treated with clozapine go on to develop metabolic syndrome at a higher rate than the general population, which predisposes them for Type 2 diabetes mellitus and cardiovascular disease. Treatments for the metabolic side-effects of clozapine vary in their efficacy. There is also a lack of knowledge about the underlying physiology of how clozapine exerts its metabolic effects in humans. In the current review, we focus on key studies which describe how clozapine affects each of the main symptoms of the metabolic syndrome, and cover some of the treatment options. The clinical data are then discussed in the context of preclinical studies that have been conducted to identify the key biological substrates involved, in order to provide a better integrated overview. Suggestions are provided about key areas for future research to better understand how clozapine causes metabolic dysregulation.


Assuntos
Clozapina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Animais , Antipsicóticos/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/epidemiologia , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/metabolismo , Fatores de Risco
12.
J Clin Psychopharmacol ; 41(2): 186-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33587389

RESUMO

BACKGROUND: Although clozapine is the gold standard for treatment-resistant schizophrenia, more than 30% of patients remain unresponsive to clozapine monotherapy and may benefit from augmentation strategies. Fluvoxamine augmentation of clozapine may be beneficial in treatment resistance because of pharmacokinetic interactions, allowing for lower clozapine dosages with higher clozapine serum levels and an increased clozapine-to-norclozapine ratio, which can modify adverse effects. An augmentation strategy using higher fluvoxamine doses may also improve persistent negative, anxiety, and obsessive-compulsive symptoms through fluvoxamine's serotonergic activity. METHODS: Through chart review, we identified 4 cases of patients with treatment-resistant psychosis who underwent high-dose fluvoxamine augmentation of clozapine to target residual negative symptoms, refractory psychosis, anxiety, and obsessive-compulsive symptoms. FINDINGS: This augmentation strategy continued in 2 patients after discharge who showed clinical improvement without significant adverse effects. Two patients experienced adverse effects that led to the fluvoxamine discontinuation. Despite the fact that fluvoxamine augmentation led to symptom improvement in only 2 patients, all patients achieved high serum clozapine levels. Hematologic parameters were monitored in all patients, and no abnormalities were observed. No severe adverse effects of clozapine were experienced. CONCLUSIONS: Although high variability of responses and adverse effects were observed during fluvoxamine augmentation to clozapine, this strategy was successful in increasing clozapine serum levels. Through fluvoxamine's serotonergic effects, this strategy may confer benefit to residual negative, obsessive, and anxiety symptoms. Limitations of this case series include the retrospective nature, absence of controls, diversity of diagnoses, multiple interventions in each patient, and lack of masked raters.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Fluvoxamina/administração & dosagem , Transtornos Psicóticos/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Clozapina/sangue , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Quimioterapia Combinada , Fluvoxamina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/fisiopatologia , Estudos Retrospectivos , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Resultado do Tratamento
13.
Med Hypotheses ; 148: 110506, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515917

RESUMO

Evidence supports the fact that clozapine can induce stressful obsessive-compulsive symptoms (OCS). Although clozapine's robust inhibition of serotonergic neurotransmission is believed to be a key mechanism underlying clozapine-induced OCS, the exact mechanism(s) are not fully understood. Intuitively, it is reasonable to believe that the dose of clozapine is likely related to emergent OCS severity. However, there is conflicting evidence where both positive and inverse relationships have been demonstrated between clozapine dose and emergent OCS severity. Upon examination of clozapine's receptor profile, in particular its affinity for 5-HT2A and D2 receptors, we hypothesize that there is a biphasic relationship between clozapine dose and emergent OCS severity. We present here a preliminary analysis of published cases in the literature to support our hypothesis.


Assuntos
Antipsicóticos , Clozapina , Transtorno Obsessivo-Compulsivo , Esquizofrenia , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Inibição Psicológica , Transtorno Obsessivo-Compulsivo/induzido quimicamente , Esquizofrenia/tratamento farmacológico
14.
PLoS One ; 16(1): e0246211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33508013

RESUMO

BACKGROUND: The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. However, there is a dearth of preclinical data that directly compares the metabolic effects of these two drugs, using sophisticated experimental procedures. The goal of the present study was to compare metabolic effects for each drug versus control animals. METHODS: Adult female rats were acutely treated with either risperidone (0.1, 0.5, 1, 2, 6 mg/kg), paliperidone (0.1, 0.5, 1, 2, 6 mg/kg) or vehicle and subjected to the glucose tolerance test; plasma was collected to measure insulin levels to measure insulin resistance with HOMA-IR. Separate groups of rats were treated with either risperidone (1, 6 mg/kg), paliperidone (1, 6 mg/kg) or vehicle, and subjected to the hyperinsulinemic euglycemic clamp. RESULTS: Fasting glucose levels were increased by all but the lowest dose of risperidone, but only with the highest dose of paliperidone. HOMA-IR increased for both drugs with all but the lowest dose, while the three highest doses decreased glucose tolerance for both drugs. Risperidone and paliperidone both exhibited dose-dependent decreases in the glucose infusion rate in the clamp, reflecting pronounced insulin resistance. CONCLUSIONS: In preclinical models, both risperidone and paliperidone exhibited notable metabolic side-effects that were dose-dependent. Differences between the two were modest, and most notable as effects on fasting glucose.


Assuntos
Antipsicóticos/toxicidade , Resistência à Insulina , Doenças Metabólicas/patologia , Palmitato de Paliperidona/toxicidade , Risperidona/toxicidade , Animais , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Doenças Metabólicas/induzido quimicamente , Modelos Animais , Ratos , Ratos Sprague-Dawley
15.
Psychol Med ; : 1-11, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33455593

RESUMO

BACKGROUND: People living in precarious housing or homelessness have higher than expected rates of psychotic disorders, persistent psychotic symptoms, and premature mortality. Psychotic symptoms can be modeled as a complex dynamic system, allowing assessment of roles for risk factors in symptom development, persistence, and contribution to premature mortality. METHOD: The severity of delusions, conceptual disorganization, hallucinations, suspiciousness, and unusual thought content was rated monthly over 5 years in a community sample of precariously housed/homeless adults (n = 375) in Vancouver, Canada. Multilevel vector auto-regression analysis was used to construct temporal, contemporaneous, and between-person symptom networks. Network measures were compared between participants with (n = 219) or without (n = 156) history of psychotic disorder using bootstrap and permutation analyses. Relationships between network connectivity and risk factors including homelessness, trauma, and substance dependence were estimated by multiple linear regression. The contribution of network measures to premature mortality was estimated by Cox proportional hazard models. RESULTS: Delusions and unusual thought content were central symptoms in the multilevel network. Each psychotic symptom was positively reinforcing over time, an effect most pronounced in participants with a history of psychotic disorder. Global connectivity was similar between those with and without such a history. Greater connectivity between symptoms was associated with methamphetamine dependence and past trauma exposure. Auto-regressive connectivity was associated with premature mortality in participants under age 55. CONCLUSIONS: Past and current experiences contribute to the severity and dynamic relationships between psychotic symptoms. Interrupting the self-perpetuating severity of psychotic symptoms in a vulnerable group of people could contribute to reducing premature mortality.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32890696

RESUMO

Longitudinal studies of cannabis exposure during early adolescence in the general population frequently report an increased risk of subsequently developing psychotic symptoms or a psychotic illness. However, there is a dearth of knowledge about the effects of early cannabis exposure on psychosis in homeless and precariously housed adults, who represent a population afflicted with high rates of psychosis. The aim of the present study was to examine how early cannabis exposure (by age 15) compared to later first use (after age 15) affected the expression of adult psychosis in this population. Secondary measures of psychopathology, drug use, cognition and brain structure were also collected. 437 subjects were recruited from single room occupancy hotels in the urban setting of the Downtown Eastside of Vancouver, Canada. Psychiatric diagnoses were determined, and psychotic symptom severity was measured with the 5-factor PANSS. Participants completed a battery of neurocognitive tests, and brain structure was assessed using structural and diffusion tensor imaging MRI scans. Results indicated that early cannabis exposure was associated with an increased risk (OR = 1.09, p < .05) of developing substance induced psychosis, whereas later first use increased risk (OR = 2.19, p < .01) of developing schizophrenia or schizoaffective disorder. There was no group difference in neurocognitive function, although differences were observed in the lateral orbitofrontal cortex and white matter tract diffusivity. These findings indicate that early cannabis exposure in this population may increase the risk of developing drug associated psychoses, which could potentially be mediated in part through altered neurodevelopmental brain changes.


Assuntos
Pessoas em Situação de Rua/psicologia , Abuso de Maconha/diagnóstico por imagem , Abuso de Maconha/psicologia , Psicoses Induzidas por Substâncias/diagnóstico por imagem , Psicoses Induzidas por Substâncias/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Adulto , Fatores Etários , Colúmbia Britânica/epidemiologia , Cannabis , Feminino , Humanos , Masculino , Abuso de Maconha/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Psicoses Induzidas por Substâncias/epidemiologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Adulto Jovem
17.
Front Psychiatry ; 11: 617428, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335492

RESUMO

Antipsychotic drugs represent the most effective treatment for chronic psychotic disorders. The newer second generation drugs offer the advantage of fewer neurological side-effects compared to prior drugs, but many cause serious metabolic side-effects. The underlying physiology of these side-effects is not well-understood, but evidence exists to indicate that the sympathetic nervous system may play an important role. In order to examine this possibility further, we treated separate groups of adult female rats acutely with either the first generation antipsychotic drug haloperidol (0.1 or 1 mg/kg) or the second generation drugs risperidone (0.25 or 2.5 mg/kg), clozapine (2 or 20 mg/kg), olanzapine (3 or 15 mg/kg) or vehicle by intraperitoneal injection. Blood samples were collected prior to drug and then 30, 60, 120, and 180 mins after treatment. Plasma samples were assayed by HPLC-ED for levels of norepinephrine, epinephrine, and dopamine. Results confirmed that all antipsychotics increased peripheral catecholamines, although this was drug and dose dependent. For norepinephrine, haloperidol caused the smallest maximum increase (+158%], followed by risperidone (+793%), olanzapine (+952%) and clozapine (+1,684%). A similar pattern was observed for increases in epinephrine levels by haloperidol (+143%], olanzapine (+529%), risperidone (+617%) then clozapine (+806%). Dopamine levels increased moderately with olanzapine [+174%], risperidone [+271%], and clozapine [+430%]. Interestingly, levels of the catecholamines did not correlate strongly with each other prior to treatment at baseline, but were increasingly correlated after treatment as time proceeded. The results demonstrate antipsychotics can potently regulate peripheral catecholamines, in a manner consistent with their metabolic liability.

18.
PLoS Med ; 17(7): e1003172, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628679

RESUMO

BACKGROUND: The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies. METHODS AND FINDINGS: A community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. CONCLUSIONS: In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.


Assuntos
Pessoas em Situação de Rua/estatística & dados numéricos , Transtornos Psicóticos/mortalidade , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adulto , Alcoolismo/mortalidade , Colúmbia Britânica/epidemiologia , Feminino , Habitação , Humanos , Estimativa de Kaplan-Meier , Masculino , Metanfetamina , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Características de Residência , Fatores de Risco , Fatores de Tempo
19.
BJPsych Open ; 6(2): e21, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043436

RESUMO

BACKGROUND: Homeless and precariously housed individuals experience a high burden of comorbid illnesses, and excess mortality. Cross-sectional studies report a high rate of cognitive impairment. Long-term trajectories have not been well investigated in this group. AIMS: To longitudinally assess risks for premature and/or accelerated cognitive ageing, and the relationship with early mortality in homeless and precariously housed people. METHOD: This is a 9-year community-based study of 375 homeless and precariously housed individuals from Vancouver, Canada. Annual cognitive testing assessed verbal learning and memory, and inhibitory control. Linear mixed-effects models examined associations between clinical risk factors (traumatic brain injury, psychotic disorders, viral exposure, alcohol dependence) and cognitive change over 9 years. Cox regression models examined the association between cognition and mortality. RESULTS: Traumatic brain injury and alcohol dependence were associated with decline in verbal memory. Inhibitory control declined, independent of risk factors and to a greater extent in those who died during the study. Better inhibitory control was associated with a 6.6% lower risk of mortality at study entry, with a 0.3% greater effect for each year of life. For each one-point increase in the Charlson Comorbidity Index score at study entry, the risk of mortality was 9.9% higher, and was consistent across age. Adjusting for comorbidities, inhibitory control remained a significant predictor of mortality. CONCLUSIONS: Findings raise the possibility of a premature onset, and accelerated trajectory, of cognitive ageing in this group of homeless and precariously housed people. Traumatic brain injury, alcohol dependence and cognition could be treatment priorities.

20.
Psychother Psychosom ; 89(3): 151-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045914

RESUMO

BACKGROUND: It is not uncommon to find obsessive-compulsive symptoms (OCS) in patients treated with clozapine. These symptoms are attributed to anti-serotonergic effects of clozapine. The objective of this study was to conduct a systematic review of reported cases of clozapine-associated OCS to better understand the nature and management of these symptoms. METHODS: MEDLINE, Embase, and PsycINFO databases were searched with no publication year or language restrictions. Studies reporting cases of clozapine-associated OCS, either de novo or exacerbation of preexisting OCS, were included. The final search date was July 11, 2019. RESULTS: Fifty-seven studies, involving 107 cases (75 de novo, 32 exacerbated OCS), were included. Clozapine triggered moderate-severe OCS at varying doses (100-900 mg/day) and treatment durations (median 6 months, interquartile range 2-24 months). Higher severity was significantly associated with preexisting OCS, poorer insight into OCS, and active psychosis at the time of OCS. Common strategies to treat clozapine-associated OCS included adding selective serotonin reuptake inhibitors, clomipramine, or aripiprazole, often accompanied by clozapine dose reduction. The rate of response to antidepressants was 49% (29/59), where younger age, shorter duration of underlying illness, shorter cloza-pine treatment duration, better insight into OCS, and presence of taboo thoughts were significantly associated with antidepressant response. Subsequent clozapine dose reduction was effective in many non-responders, where aripiprazole was simultaneously added in 50% (8/16). CONCLUSIONS: Clozapine can trigger severe OCS. Adding aripiprazole with/without clozapine dose reduction may be a good alternative to antidepressants for managing clozapine-associated OCS. Clinicians should be more vigilant about these adverse effects and administer appropriate treatments.

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