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1.
Cells ; 10(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525562

RESUMO

Lithium salts have been in the therapeutic toolbox for better or worse since the 19th century, with purported benefit in gout, hangover, insomnia, and early suggestions that lithium improved psychiatric disorders. However, the remarkable effects of lithium reported by John Cade and subsequently by Mogens Schou revolutionized the treatment of bipolar disorder. The known molecular targets of lithium are surprisingly few and include the signaling kinase glycogen synthase kinase-3 (GSK-3), a group of structurally related phosphomonoesterases that includes inositol monophosphatases, and phosphoglucomutase. Here we present a brief history of the therapeutic uses of lithium and then focus on GSK-3 as a therapeutic target in diverse diseases, including bipolar disorder, cancer, and coronavirus infections.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/metabolismo , Coronavirus/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Compostos de Lítio/farmacologia , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Medicine (Baltimore) ; 99(42): e22823, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080761

RESUMO

INTRODUCTION/RATIONALE: Multiple sclerosis (MS) is associated with a higher prevalence of mood and psychiatric disorders, such as bipolar disorder (BD). While mania is most often associated with BD, MS can also induce manic symptoms. However, it is crucial to distinguish which condition is causing mania since medical management is different based on its etiology. Herein, we report a case of a manic episode in a middle-aged female with a prolonged history of BD who received a recent diagnosis of MS 1 year ago. PATIENT CONCERNS: A 56-year-old female presented with an episode of mania and psychosis while receiving a phenobarbital taper for chronic lorazepam use. She had a prolonged history of bipolar type 1 disorder and depression. She showed optic neuritis and was diagnosed with MS a year prior. DIAGNOSES: The patient was diagnosed with BD-induced mania based on the absence of increased demyelination compared to previous MRI and lack of new focal or lateralizing neurologic findings of MS. INTERVENTIONS: Lithium was given for mood stabilization and decreased dosage of prior antidepressant medication. Risperidone was given for ongoing delusions. OUTCOMES: After 8 days of hospitalization, patient's mania improved but demonstrated atypical features and ongoing delusions. She was discharged at her request to continue treatment in an outpatient setting. CONCLUSION/LESSON: In BD patients with an episode of mania, MS should be included in the differential, since both conditions can cause manic symptoms. The origin of mania should be delineated through a detailed neurological exam, neuroimaging, and thorough patient-family psychiatric history for appropriate clinical treatment.


Assuntos
Transtorno Bipolar/psicologia , Esclerose Múltipla/psicologia , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Pessoa de Meia-Idade , Risperidona/uso terapêutico
3.
J Clin Psychiatry ; 81(5)2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32841553

RESUMO

OBJECTIVE: Lithium is an important mood disorder treatment; however, the renal risks of its use in older adults are unclear. We wished to determine in older adults (1) whether lithium is associated with increased risk of renal decline compared to valproate and (2) whether this association differs with higher vs lower baseline serum lithium concentrations. METHOD: We conducted a population-based cohort study using linked health care databases (Ontario, Canada). The cohort consisted of older adults (mean age 71 years) accrued 2007-2015; 3,113 lithium users were propensity-score matched 1:1 to 3,113 valproate users. Users with higher (> 0.7 mmol/L) or lower concentration of serum lithium were further examined. The primary outcome was ≥ 30% loss in estimated glomerular filtration rate from baseline. RESULTS: Matched lithium users and valproate users demonstrated similar indicators of baseline health over a median (maximum) follow-up of 3.1 (8.3) years. Lithium was associated with increased risk of renal function loss compared to valproate (674/3,113 [21.7%] vs 584/3,113 [18.8%]; 6.5 vs 5.7 events per 100 person years; hazard ratio = 1.14 [95% CI = 1.02-1.27]). When baseline serum lithium concentrations were > 0.7 mmol/L, the risk of renal decline compared to valproate use was 1.26 (95% CI = 1.06-1.49); when baseline lithium concentrations were ≤ 0.7 mmol/L, the risk was 1.06 (95% CI = 0.92-1.22). CONCLUSION: In older adults, lithium use is associated with a statistically significant increased risk of renal decline compared to valproate use, although the decline is less than previously reported. Further studies should confirm whether this effect is primarily in patients with higher serum lithium concentrations.


Assuntos
Antimaníacos/uso terapêutico , Lítio/uso terapêutico , Insuficiência Renal/induzido quimicamente , Idoso , Antimaníacos/efeitos adversos , Antimaníacos/sangue , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Lítio/efeitos adversos , Lítio/sangue , Estudos Longitudinais , Masculino , Pontuação de Propensão , Fatores de Risco , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico
4.
Neuron ; 106(5): 715-726, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32497508

RESUMO

Ketamine exerts rapid antidepressant action in depressed and treatment-resistant depressed patients within hours. At the same time, ketamine elicits a unique form of functional synaptic plasticity that shares several attributes and molecular mechanisms with well-characterized forms of homeostatic synaptic scaling. Lithium is a widely used mood stabilizer also proposed to act via synaptic scaling for its antimanic effects. Several studies to date have identified specific forms of homeostatic synaptic plasticity that are elicited by these drugs used to treat neuropsychiatric disorders. In the last two decades, extensive work on homeostatic synaptic plasticity mechanisms have shown that they diverge from classical synaptic plasticity mechanisms that process and store information and thus present a novel avenue for synaptic regulation with limited direct interference with cognitive processes. In this review, we discuss the intersection of the findings from neuropsychiatric treatments and homeostatic plasticity studies to highlight a potentially wider paradigm for treatment advance.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Homeostase/efeitos dos fármacos , Ketamina/farmacologia , Compostos de Lítio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Animais , Antimaníacos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Ketamina/uso terapêutico , Compostos de Lítio/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Sinapses/efeitos dos fármacos
5.
Psychiatry Res ; 286: 112865, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114208

RESUMO

Bipolar disorder (BD) may be associated with accelerated cellular aging. However, previous studies on telomere length (TL), an important biomarker of cellular aging, have yielded mixed results in BD. We aimed to evaluate the hypothesis that BD is associated with telomere shortening and whether this is counteracted by long-term lithium treatment. We also sought to determine whether long-term lithium treatment is associated with increased expression of telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. We determined TL and TERT expression in 100 BD I patients and 100 healthy controls. We also genotyped three single nucleotide polymorphisms associated with TL. TERT expression was significantly increased in BD I patients currently on lithium treatment. TERT expression was also significantly positively correlated with duration of lithium treatment in patients treated for 24 months or more. However, we did not find any significant effect of lithium treatment on TL. Neither did we find significant differences in TL between BD patients and controls. We suggest that long-term lithium treatment is associated with an increase in the expression of TERT. We hypothesize that an increase in TERT expression may contribute to lithium's mood stabilizing and neuroprotective properties by improving mitochondrial function and decreasing oxidative stress.


Assuntos
Envelhecimento/metabolismo , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/genética , Senescência Celular/genética , Compostos de Lítio/uso terapêutico , Lítio/uso terapêutico , Telomerase/metabolismo , Adulto , Envelhecimento/genética , Transtorno Bipolar/sangue , Senescência Celular/efeitos dos fármacos , Feminino , Humanos , Compostos de Lítio/farmacologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Telomerase/efeitos dos fármacos , Telomerase/genética , Telômero/efeitos dos fármacos , Telômero/genética , Telômero/metabolismo , Homeostase do Telômero/genética , Encurtamento do Telômero/efeitos dos fármacos , Encurtamento do Telômero/genética
6.
Psychiatr Clin North Am ; 43(1): 167-186, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008683

RESUMO

Despite the relatively high prevalence of mixed symptoms and features among patients with mood disorders, the current literature supporting the specific efficacy of second-generation antipsychotics and mood stabilizers for the treatment of mixed symptoms is limited. Several studies have demonstrated that acute affective episodes with mixed symptoms or features tend to respond unsatisfactory to treatments that are usually more effective for the management of other affective phases. There is clearly a need for clinical trials in order to determine the more adequate pharmacologic option for the treatment of individuals suffering from affective episodes with mixed features.


Assuntos
Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtornos do Humor/tratamento farmacológico , Humanos
7.
Psychiatr Clin North Am ; 43(1): 95-111, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008691

RESUMO

Pediatric bipolar disorder (PBD) is a severe and chronic illness. The occurrence of mixed symptoms might add further risk of recurrence of treatment resistance and suicidality. Early recognition and treatment of mixed symptoms might prevent illness progression and development of suicide attempts. This article provides an update on the epidemiology, clinical profile, and treatment of youth with PBD with mixed states. Mixed states in PBD are characterized by higher rates of suicide and more chronic symptoms, and are associated with younger age of onset and greater comorbidity. A careful assessment for mixed states using standardized criteria is essential.


Assuntos
Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Adolescente , Criança , Pré-Escolar , Transtorno Depressivo Maior/complicações , Feminino , Humanos , Masculino , Tentativa de Suicídio , Adulto Jovem
8.
PLoS One ; 15(1): e0227217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923220

RESUMO

BACKGROUND: Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD. METHODS: This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ≤ 6), and good response (GR; Alda total score ≥ 7). RESULTS: Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001). CONCLUSION: The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity.


Assuntos
Alcoolismo/epidemiologia , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Lamotrigina/uso terapêutico , Compostos de Lítio/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto , Comorbidade , Feminino , Seguimentos , Humanos , Compostos de Lítio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seul/epidemiologia , Resultado do Tratamento
10.
J Affect Disord ; 260: 366-371, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539672

RESUMO

BACKGROUND: Low rates of medication adherence remain a major challenge across psychiatry. In part, this likely reflects patient concerns about safety and adverse effects, accurate or otherwise. We therefore sought to characterize online information about common psychiatric medications in terms of positive and negative sentiment. METHODS: We applied a natural language processing tool to score the sentiment expressed in web search results for 51 psychotropic medications across 3 drug classes (antidepressants, antipsychotics, and mood stabilizers), as a means of seeing if articles referencing these medications were generally positive or generally negative in tone. We compared between medications of the same class, and across medication classes. RESULTS: Across 12,733 web search results, significant within-class differences in positive (antidepressants: F(24,2682) = 2.97, p < 0.001; antipsychotics: F(16,4029) = 3.25, p < 0.001; mood stabilizers: F(8,2371) = 6.88, p < 0.001) and negative sentiment (antidepressants: F(24,6282) = 11.17, p < 0.001; antipsychotics: F(16, 4029)  = 12.13, p < 0.001; mood stabilizers: F(8, 2371) = 13.28, p < 0.001) were identified. Among these were significantly greater negative sentiment for the antidepressants sertraline, duloxetine, venlafaxine, and paroxetine, and for the antipsychotics, quetiapine and risperidone. Conversely, lithium preparations and valproate exhibited less negative sentiment than other mood stabilizing medications. LIMITATIONS: While these results provide a novel means of comparing medications, the present analyses cannot be linked to individual patient consumption of this information, or to its influence on their future clinical interactions. CONCLUSIONS: Overall, a subset of psychotropic medications were associated with significantly more negative sentiment. Characterizing these differences may allow clinicians to anticipate patient willingness to initiate or continue medications.


Assuntos
Informação de Saúde ao Consumidor/estatística & dados numéricos , Internet/estatística & dados numéricos , Processamento de Linguagem Natural , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Feminino , Humanos , Masculino , Adesão à Medicação/psicologia , Psiquiatria/tendências
11.
J Affect Disord ; 260: 361-365, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539671

RESUMO

OBJECTIVE: Misdiagnosis is common in bipolar disorder and disproportionally affects racial and ethnic minorities. There is interest in better understanding the contribution of differential symptomatic illness presentation to misdiagnosis. METHODS: Utilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African vs European ancestry (AA = 415 vs EA = 480). The Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate symptom endorsement contributing to diagnostic confirmation of bipolar I disorder (BPI) and lifetime medication use. RESULTS: Elevated/euphoric mood was less endorsed in AA vs EA participants (p = 0.03). During the most severe episode of mania, AA participants, in comparison to EA participants, had a lower sum of manic symptoms (p = 0.006) and a higher rate of hallucinations (p = 0.01). During lifetime psychosis, AA participants, in comparison to EA participants, had a higher lifetime sum of delusions (p = 0.01) and hallucinations (p < 0.0001). AA participants reported lower use of lithium (p < 0.0001) and mood stabilizing anticonvulsants (p = 0.0003). CONCLUSIONS: The differential rate of manic and psychotic symptom endorsement from a semi-structured diagnostic interview may represent differential illness presentation based on biological differences or racial or study biases (e.g. ascertainment). Increased minority recruitment in bipolar research is therefore a necessary future direction. LIMITATIONS: Recall and interviewer bias may affect study results, but are likely diminished by the alignment of symptom endorsement and medication use.


Assuntos
Grupo com Ancestrais do Continente Africano/psicologia , Antimaníacos/uso terapêutico , Transtorno Bipolar/etnologia , Grupo com Ancestrais do Continente Europeu/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adulto , Anticonvulsivantes/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Bases de Dados Factuais , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estados Unidos
12.
Int Clin Psychopharmacol ; 35(1): 8-18, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31609786

RESUMO

Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management.


Assuntos
Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Fatores Etários , Antidepressivos/administração & dosagem , Antimaníacos/administração & dosagem , Antipsicóticos/administração & dosagem , Transtorno Bipolar/classificação , Manual Diagnóstico e Estatístico de Transtornos Mentais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Estados Unidos
13.
Expert Opin Pharmacother ; 21(1): 47-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693423

RESUMO

Introduction: The treatment of borderline personality disorder (BPD) remains an open question for clinicians. There is scarce evidence available and the guidelines' conclusions diverge. Together with these factors, the complexity of BPD generates uncertainty in day-to-day practice. This narrative review aims to provide an overview of advances in BPD treatment and posit a critical opinion based on clinical evidence and practice.Areas covered: The authors review the clinical trials concerning the efficacy of the main classes of drugs in BPD: antidepressants, mood stabilizers, first-, second-, and third-generation antipsychotics, and other agents (opiate antagonists, clonidine, oxytocin, omega-3 fatty acids). They also include in this review studies on combinations of drugs and psychotherapies.Expert opinion: An individualized, tailored pharmacotherapy for BPD that targets the prominent symptom clusters can improve relevant aspects of the clinical picture. However, no medication is indicated to treat the global psychopathology of BPD. Polypharmacy should be avoided or strictly limited. To date, pharmacotherapy alone does not suffice to manage the complexity of BPD. Combining medication with psychotherapy may improve specific BPD symptom dimensions. In particular, it may help those aspects that respond slowly or not at all to monotherapy.


Assuntos
Transtorno da Personalidade Borderline/terapia , Psicoterapia/métodos , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Polimedicação
14.
J Clin Psychopharmacol ; 40(1): 18-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31804452

RESUMO

BACKGROUND: Attitudes toward medication treatment are thought to significantly influence adherence in bipolar disorder (BD) and schizophrenia. However, the actual impact of patients' treatment attitudes on adherence and determinants of attitudes is still uncertain. METHODS: A longitudinal examination of treatment attitudes and their correlates was conducted among patients with BD and their caregivers compared with those with schizophrenia. Structured assessments of symptom severity, functioning, insight, medication side effects, knowledge of illness, medication adherence, treatment attitudes, and treatment satisfaction were performed among 176 selected patients (106 with BD and 70 with schizophrenia) and their caregivers. Participants were reassessed on these parameters at 3 and 6 months. RESULTS: Rates of nonadherence at baseline varied widely between self-reports, clinician ratings, and serum levels. Though symptoms and functioning improved with treatment, overall rates of nonadherence increased in the first 3 months because of early dropouts and remained stable thereafter. However, treatment attitudes and treatment satisfaction remained largely unchanged among patients and caregivers. Both positive and negative attitudes were commonly held and patients' attitudes did not differ between BD and schizophrenia. Patients' attitudes were significantly associated with adherence, insight, knowledge about illness, treatment satisfaction, symptom severity, social disadvantage, and side effects together with caregivers' knowledge, attitudes, and satisfaction. Caregivers of patients with schizophrenia were more knowledgeable and had more positive attitudes than patients. CONCLUSIONS: Patients' attitudes to medication treatment are associated with adherence over time. They are relatively enduring and mainly associated with insight, knowledge of illness, and treatment satisfaction among patients and their caregivers. These findings could inform psychosocial interventions aiming to improve treatment attitudes and adherence in BD and schizophrenia.


Assuntos
Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Cuidadores/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Pacientes/psicologia , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Antimaníacos/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Feminino , Humanos , Índia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Fatores Socioeconômicos , Fatores de Tempo , Adulto Jovem
16.
Food Chem Toxicol ; 136: 110986, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760073

RESUMO

It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e., lithium and valproate) modulate IDO to protect against AMPH-induced mania-like behaviors. AMPH-induced IDO-1 expression was significantly greater than IDO-2 expression in the prefrontal cortex of wild type mice. IDO-1 expression was more pronounced in the mitochondria than in the cytosol. AMPH treatment activated intra-mitochondrial Ca2+ accumulation and mitochondrial oxidative burden, while inhibited mitochondrial membrane potential and activity of the mitochondrial complex (I > II), mitochondrial glutathione peroxidase, and superoxide dismutase, indicating that mitochondrial burden might be contributable to mania-like behaviors induced by AMPH. The behaviors were significantly attenuated by lithium, valproate, or IDO-1 knockout, but not in IDO-2 knockout mice. Lithium, valproate administration, or IDO-1 knockout significantly attenuated mitochondrial burden. Neither lithium nor valproate produced additive effects above the protective effects observed in IDO-1 KO in mice. Collectively, our results suggest that mood stabilizers attenuate AMPH-induced mania-like behaviors via attenuation of IDO-1-dependent mitochondrial stress, highlighting IDO-1 as a novel molecular target for the protective potential of mood stabilizers.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Lítio/uso terapêutico , Ácido Valproico/uso terapêutico , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/metabolismo , Cálcio/metabolismo , Dextroanfetamina , Glutationa Peroxidase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Locomoção/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Córtex Pré-Frontal/patologia , Superóxido Dismutase/metabolismo
17.
BMC Psychiatry ; 19(1): 393, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830934

RESUMO

BACKGROUND: The purpose of this study was to assess the pharmacological treatment strategies of inpatients with borderline personality disorder between 2008 and 2012. Additionally, we compared pharmacotherapy during this period to a previous one (1996 to 2004). METHODS: Charts of 87 patients with the main diagnosis of borderline personality disorder receiving inpatient treatment in the University Medical Center of Goettingen, Germany, between 2008 and 2012 were evaluated retrospectively. For each inpatient treatment, psychotropic drug therapy including admission and discharge medication was documented. We compared the prescription rates of the interval 2008-2012 with the interval 1996-2004. RESULTS: 94% of all inpatients of the interval 2008-2012 were treated with at least one psychotropic drug at time of discharge. All classes of psychotropic drugs were applied. We found high prescription rates of naltrexone (35.6%), quetiapine (19.5%), mirtazapine (18.4%), sertraline (12.6%), and escitalopram (11.5%). Compared to 1996-2004, rates of low-potency antipsychotics, tri-/tetracyclic antidepressants and mood stabilizers significantly decreased while usage of naltrexone significantly increased. CONCLUSIONS: In inpatient settings, pharmacotherapy is still highly prevalent in the management of BPD. Prescription strategies changed between 1996 and 2012. Quetiapine was preferred, older antidepressants and low-potency antipsychotics were avoided. Opioid antagonists are increasingly used and should be considered for further investigation.


Assuntos
Transtorno da Personalidade Borderline/tratamento farmacológico , Transtorno da Personalidade Borderline/epidemiologia , Psicotrópicos/uso terapêutico , Adulto , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno da Personalidade Borderline/psicologia , Feminino , Alemanha/epidemiologia , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/uso terapêutico , Prevalência , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
Curr Drug Res Rev ; 11(2): 85-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875781

RESUMO

BACKGROUND: The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer's disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown. OBJECTIVE: On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence. CONCLUSION: It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3ß in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3ß inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Estimulantes do Sistema Nervoso Central , Compostos de Lítio/farmacologia , Compostos de Lítio/uso terapêutico , Metanfetamina , Animais , Antimaníacos/farmacologia , Antimaníacos/uso terapêutico , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos
19.
BMC Pharmacol Toxicol ; 20(1): 71, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783774

RESUMO

BACKGROUND: Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis. CASE PRESENTATION: The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations. CONCLUSION: Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Pancreatite/induzido quimicamente , Ácido Valproico/efeitos adversos , Amilases/sangue , Amilases/urina , Antimaníacos/administração & dosagem , Antimaníacos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/terapia , Resultado do Tratamento , Ácido Valproico/administração & dosagem , Ácido Valproico/uso terapêutico
20.
BMJ Case Rep ; 12(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678916

RESUMO

A young man with neuropsychiatric problems has a small 22q13.33 duplication. We suggest this causes his condition. His disorder may represent a 22q13.33 behavioural phenotype. In childhood, he was diagnosed with mild intellectual disability. He was later diagnosed with Tourette syndrome, atypical autism spectrum disorder and bipolar disorder. Lithium seems effective in treating his affective symptoms. He has mild dysmorphic features, full lips and protruding ears. An array comparative genomic hybridisation showed a 300 kb duplication. The duplication harbours several genes, notably SH3 and multiple ankyrin repeat domain 3 (SHANK 3). The small size helps focus on a critical region for a 22q13.33 duplication syndrome. Mutations, deletions and duplications should be kept in mind as causes of neuropsychiatric disorders, especially in a patient with dysmorphic traits.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno Bipolar/diagnóstico , Transtornos Cromossômicos/diagnóstico , Deficiência Intelectual/diagnóstico , Síndrome de Tourette/diagnóstico , Antimaníacos/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Deleção Cromossômica , Transtornos Cromossômicos/complicações , Cromossomos Humanos Par 22 , Humanos , Deficiência Intelectual/complicações , Compostos de Lítio/uso terapêutico , Masculino , Proteínas do Tecido Nervoso/genética , Síndrome de Tourette/complicações , Síndrome de Tourette/tratamento farmacológico , Adulto Jovem
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