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An Antipsychotic?

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An Antipsychotic? The ABCDs of Overcoming Roadblocks to recovery in First episode psychosis Matcheri S Keshavan MD MAPNET, Beth Israel Deaconess Medical Center, Massachusetts Mental Health Center and Harvard Medical School MH 64023; 60902; 92440, Commonwealth Research Center and a FEPTAC grant by DMH. No other relevant disclosures STAGES OF RECOVERY Worse Stage 1: Symptom stabilization Better Stage 2: Functional Stage 3: recovery Acceptance, Integration Worse Weeks Months Years Key points • What are the outcome trajectories in schizophrenia? • How can we predict outcome? – Non-malleable – Malleable • How we can overcome these obstacles? • Summary and next steps The Kraepelinian pessimism of Dementia praecox And Bleulerian optimism The patient may never achieve restitutio ad integrum Bleuler 1911 The sooner patients can be restored to an earlier life and the less They are allowed to withdraw into the world of their own ideas, The sooner do they become socially functional Bleuler 1908 Outcome in schizophrenia is variable Single Episode, full remission 40% Episodic, without Inter-episode deficits Episodic, w/inter-episode 30% deficits Chronic, Persistent/ 30% Ciompi, Bleuler, Jablenski declining Outcome can be improved by appropriate intervention at any phase of illness The “snowballing effect” in the course of schizophrenia Premorbid deficits Negative family and societal response Prodromal Psychotic/ negative sx Ist psychotic episode Sec negative Stresses of adolescence Untreated Sx “Neurotoxicity” Fear, denial, Stigma, Substance abuse Relapse Med side effects, Substance abuse Poor insight Cognitive impairment Noncompliance Predictors of outcome • Outcome trajectories in schizophrenia • How can we Predict outcome? – Non-malleable – Malleable • Adherence • Brain and cognition • Cannabis and other substance misuse • Delay in Treatment (DUP) • Can we influence outcome of psychotic disorders? • Summary and next steps Gender: no differences in outcome Race : African Americans may SEX*"timept1"; LS Means have poorer outcome Wilks lambda=.98706, F(10, 1752)=1.1443, p=.32487 70 RACE*"timept1"; LS Means Wilks lambda=.97829, F(10, 1600)=1.7658, p=.06201 65 Effective hypothesis decomposition Vertical bars denote 0.95 confidence intervals 60 70 65 55 172 males and 60 50 100 females 55 GAS 45 50 40 GAS 45 35 40 30 35 SEX 1 30 25 SEX BASELINE WK04 WK26 YR1 YR2 YR4 RACE 2 25 timept1 BASELINE WK04 WK26 YR1 YR2 YR4 1 RACE timept1 2 A diagnosis of schizophrenia predicts a poorer outcome DIAGMAX*"timept1"; LS Means Wilks lambda=.95356, F(15, 2501.5)=2.8974, p=.00015 Effective hypothesis decomposition Vertical bars denote 0.95 confidence intervals 80 75 Pittsburgh 70 First episode 65 60 Non-Schiz psychoses n=95 Longitudinal 55 GAS 50 Study 45 Schiz psychoses n=175 40 35 30 DIAGMAX 25 BASELINE WK04 WK26 YR1 YR2 YR4 1 DIAGMAX Non-malleable predictors timept1 2 Reversible predictors: Early Adherence Predicts Subsequent Adherence During Follow-up in First Episode 1. Adherence to treatment Psychoses 120 p= .000025 .000155 .0024 .0005 100 80 60 40 20 Compliance rating Compliance 0 Follow-up 6 months 12 months 24 months 48 months Good (>80%) adherence at 4 weeks) Keshavan et al Poor (<80%) adherence at 4 weeks) unpublished Impaired neurocognition Reversible predictors: strongly points to brain dysfunction early in 2. Brain and cognition schizophrenia Neuropsychological performance in early schizophrenia, psychotic and non-psychotic depression nd healthy comparison subjects (Hill, Keshavan et al AJP 2004) Frontotemporal gray matter loss predicts poor outcome in schizophrenia Prasad et al Prog Neuropharmacol Biol Psychiatry 2005 Wojtalik JA1, Smith MJ2, Keshavan MS3, Eack SM1,4. A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia. Schizophr Bull. 2017 Wood et al 2006 Reversible predictors:3. Cannabis and other drugs of misuse. Cannabis abuse predicts relapse and Brain dysfunction non-adherence mediates this effect Schoeler, et al Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first-episode psychosis: (n=397) a prospective analysis Lancet Psychiatry. 2017 Schiz Res 2009 Intermittent and persistent users have lower rates of remission in FEP On-off users Continuous users N=301) Weibel et al Schiz Bulletin 2017 Frequency of conversion from SIP to schizophrenia is Highest with cannabis abuse Alderson and Lawrie Psychological Medicine 2017 Prolonged Illness duration predicts poor outcome in first episode psychoses Keshavan et al Schizophrenia Bulletin 2003 40 35 Partial r=-.39; p=.001 30 25 20 15 10 5 0 ILLNESS DURATION FROM PRODROME (SQRT WKS) ILLNESS DURATION FROM PRODROME -5 4 6 8 10 12 14 16 18 STRAUSS CARPENTER OUTCOME SCORE AT 1 YEAR Reversible predictors: 4. Delay in treatment Neuroreport 2009 Summary: Roadblocks to recovery Delay in treatment c c Brain and Cannabis and other drugs cognitive c Poor dysfunction recovery c Adherence, lacking Determinants of outcome • Outcome trajectories in schizophrenia • Predictors of outcome – Non-malleable – Malleable • How can we overcome these reversible roadblocks? • Summary Model of Care Recognition & Assessment Screening Case manager, psychiatrist Psychosocial Research Management Staff Coordinated . work Symptoms, side Specialty Care effects, quality of life, genetic, . school etc.) . Neuropsychologist relationships TREATMENT Medical Management Psychotherapy Individual Family Cognitive Group intervs. Family Education remediation Intervention Modules Approaches to enhance adherence • Patient who refuses meds • Improve therapeutic alliance; rapid acting meds; involuntary meds as last resort • Patient non-adherent because • Dosage adjustment; consider meds not working medication switch, clozapine • Patient non-adherent because • Dosage adjustment; consider of side effects medication switch; monitor & educate re. Side effects • Patient does not show up for • Improve hospital to clinic first appointment continuity; make care more accessible and patient friendly • Patient who frequently • Cues to remember; memory aids misses/forgets meds/appts such as pillboxes and alarm watches; phone call reminders; Long acting injections, digital pills • Patient who believes he/she • Compliance therapy; continuing does not need meds psychoeducation; cognitive remediation CET is effective in chronic schizophrenia .. as well as early course schizophrenia Hogarty.. et al Arch Gen Psy 2004; Eack…Keshavan J Psychiatric Services 2009 Psychosocial treatments can Harness brain plasticity early in those at risk to protect against gray matter loss, and to build “reserve” Eack et al Arch Gen Psychiatry 2010 Treatments for comorbid cannabis abuse Psychoeducation Cognitive-behavioral therapy Contingency management Motivational enhancement therapy Cognitive enhancement therapy No pharmacologic agents approved Early detection improves long term outcome in psychotic disorders Hegelstad et al 2012 Am J psychiatry Conclusions • Outcome trajectories are variable, and increasingly optimistic in schizophrenia • Predictors of outcome can be non-malleable but many are reversible. Brain structure and function mediate outcome, and are plastic, potentially reversible • Outcome of psychotic disorders is likely to be favorably impacted by early integrated intervention. Each of the reversible roadblocks (Adherence, Brain reserve, Cannabis and treatment Delay) can be overcome, and leads to improved outcomes • Symptomatic and functional recovery are not enough, and the goal has to include full personal recovery and integration Marijuana Legalization David L. Hoffman, M.D., M.F.A. Medical Director, Metro Boston Area Massachusetts Dept. of Mental Health Objectives By the conclusion of this presentation, participants will be knowledgeable about: • The legal history of federal marijuana laws and regulations • The current status of regulations regarding medical and recreational marijuana in Massachusetts • Current Federal position regarding marijuana • Experience of states that have legalized marijuana • Challenges related to driving under the influence of marijuana • Significant issues involving the DMH service system created by the new medical and recreational marijuana regulations Disclosures • I have no conflict of interest or commercial involvement in any products discussed in this presentation. U.S. Regulatory History of Marijuana - 1 • Widespread unregulated medicinal use until early 20th century. • 1st U.S restriction in Washington, D.C. in 1906 • In 1911 Massachusetts restricted sale of marijuana, requiring a prescription and classifying it as a habit-forming substance. • The Uniform State Narcotic Act (1925-1932) encouraged all states to regulate cannabis use. • Federal Bureau of Narcotics established in 1930. • 1937 Marihuana Tax Act prohibited all types of hemp production in U.S. and made marijuana illegal except for medical or industrial use. U.S. Regulatory History of Marijuana - 2 • 1970 - Controlled Substances Act, the federal drug policy under which the manufacture, importation, possession, use and distribution of certain substances, including marijuana, is regulated. • 1973 – Drug Enforcement Agency (DEA) established. The DEA is a Department of Justice federal law enforcement agency tasked with combating drug smuggling and use in the U.S. Schedules of Controlled Substances • Placing a drug or other substance in a certain Schedule or removing it from a certain Schedule is primarily based on 21 USC §§ 801 • Every schedule otherwise requires finding and specifying
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