Mood Disorders and Addictions: A shared biology?

Transcription

1 Mood Disorders and Addictions: A shared biology? Dr. Paul Stokes Clinical Senior Lecturer, Centre for Affective Disorders, Department of Psychological Medicine

2 Disclosures No relevant disclosures: No paid lectures for pharmaceutical companies No membership of industry advisory boards No shareholdings in pharmaceutical companies No current or previous industry grant income

3 Overview 1. Prevalence of co-morbid addictions in mood disorders 2. Impact on clinical outcomes in bipolar disorder 3. Mechanisms Dopamine and reward GABA-A dysfunction 4. Treatment Mood stabilisers Atypical antipsychotics

4 PREVALENCE

5 Lifetime prevalence of addiction in mood disorders X % Lifetime prevalence Odds Ratio ECA study Regier et al JAMA 1990

6 Lifetime prevalence of alcohol dependence in mood disorders X Normal Unipolar MDD Bipolar 1 Bipolar 2 Schizophrenia Anxiety disorders % Alcohol dependence Odds ratio ECA study Regier et al JAMA 1990

7 Risk of alcohol dependence in bipolar disorder higher for women than men Frye et al. Am J Psychiatry 2003

8 Lifetime prevalence of any drug dependence in mood disorders X % Drug dependence Odds ratio Normal Unipolar MDD Bipolar 1 Bipolar 2 Schizophrenia Anxiety disorders ECA study Regier et al JAMA 1990

9 Lifetime prevalence of comorbid drug abuse in bipolar disorder Prevalence estimates vary widely between individual drug classes Bipolar Disorder Cocaine: 6%-39% Cannabis: 15%-64% Opiates: 3%-25% Sedatives: 5%-31% UK national population Cocaine: 9% Cannabis: 31% Opiates: 1% Sedatives: 3% Cassidy et al. Bipolar Disorders 2001 British Crime Survey, Home Office, UK

10 Bipolar disorder and nicotine addiction US National Comorbidity survey found that Bipolar Disorder had the highest rates of cigarette smoking of any mental disorder: Bipolar Disorder 3x higher rates MDD 1.5 x increased rates Non affective psychosis 2 x higher rates Lasser et al JAMA 2000

11 Behavioural addiction symptoms more common in Bipolar disorder: 33% reach cut off for at least one behavioural addiction Significantly higher rating scale scores for: Pathological gambling Compulsive buying Sexual and work addiction Di Nicola et al Journal of Affective Disorders 2010

12 Zurich Cohort study (20 year follow-up): Manic symptoms associated with: 4x risk of alcohol dependency 5x risk of cannabis abuse/dependence 11x risk of benzodiazepine abuse/dependence BP2 associated with: 21 x risk of alcohol dependence 14x risk of benzodiazepine abuse/dependence No increased risk of cannabis dependence Merikangus et al Archives Gen Psychiatry 2008

13 IMPACT ON CLINICAL OUTCOMES

14 Alcohol misuse associated with more severe mania Acute mania complicated by current alcohol misuse associated with: Higher numbers of manic symptoms Increased risk profile: More mood lability Higher impulsivity levels Increased risk of violence Increased rates of other drug abuse Salloum et al Bipolar Disorders 2002

15 Remission after an episode of mania less likely in patients with prior substance use Particularly alcohol or cannabis use Remission more likely in those treated with Valproate or Carbamezepine than Lithium Goldberg et al J Clin Psych 1999

16 Co-morbid drug use increases risk of suicide in Bipolar Disorder % Suicide attempts Overall Drug use disorder No drug use Dalton et al. Bipolar Disorders 2003

17 Other impacts Co-morbid substance use disorders in bipolar disorder associated with: Poorer adherence to medication (Keck et al. 1998) Poorer outcomes (Keck et al. 1998) Higher relapse rates (Tohen et al 1990) Probability of not relapsing over 4 years in 24 first episode BD patients (Tohen et al 1990)

18 A shared neurobiology?: Hypotheses 1. Dopamine and reward 2. GABA dysfunction

19 MECHANISMS: DOPAMINE

20 Young men who reported high rates of hypomanic symptoms (Bipolar Phenotype) show blunted subjective responses to alcohol: Significantly lower intoxication effects from alcohol Higher expectation of positive effect of alcohol Similar low level response to alcohol found in those at high risk of developing alcohol dependence (Volavka et al 1996; Schuckit and Smith 1996) Yip et al Neuropsychopharmacology 2012

21 Casey et al Biological Psych 2013

22 Blunted dopamine release recently found in patients with schizophrenia and substance dependence after an amphetamine challenge Thompson et al Molecular Psychiatry 2013

23 Key Question Are those at risk of developing bipolar disorder also at high risk for addictions due to a blunted dopamine response to reward?

24 MECHANISMS: GABA

25 High rates of co-morbid GAD in mood disorders Patients with mood disorders have 14 x greater risk of generalised anxiety disorder: MDD: 6x Bipolar 1: 9x Bipolar 2: 5x Grant et al Psychological Medicine 2005

26 GABA-A receptor availability reduced in anxiety disorders GAD: Tiihonen et al 1997 GAD PTSD: Bremner et al Am J Psychiatry 2000 Panic: Malizia et al Arch Gen Psych 1998

27 Key Question Are patients with mood disorders self medicating with alcohol, cannabis and nicotine to compensate for a deficit in the GABA system?

28 TREATMENT: MOOD STABILISERS

29 How to treat pharmacologically? Lithium May not be effective in bipolar variants such as dysphoric, mixed, or rapid cycling, which are overrepresented in bipolar alcoholic patients. Lithium carbonate was ineffective in decreasing alcohol consumption in a large multicenter trial of depressed alcoholics (Dorus et al JAMA 1989)

30 24 week trial in Bipolar 1 patients & alcohol dependence All received treatment as usual : Li, detox if necessary, psychosocial interventions for SUD Valproate group had Less heavy drinking ; related to valproate plasma levels; improved GGT in Valproate group No difference in improvement of symptoms of mania or depression between groups Salloum et al. Am J Psych 2005

31 Most patients did not stabilize (31 vs 118) difficult trial to do / condition Alcohol, cocaine, cannabis dependence or abuse. BPD responders more likely to be no longer abusing drugs No difference in primary outcome : relapse to new mood episode Kemp et al., J Clin Psychiatry (1)

32 Open label study of effect of 300mg lamotrigine on mood and cocaine use Improvements in: Depression and mania symptoms (HAMD, YMRS scores) Cocaine craving Dollars spent per week on cocaine Sherwood Brown et al J Affect Disorders 2006

33 TREATMENT: ANTIPSYCHOTICS

34 Heavy drinking CGI Randomised to lithium or valproate, then randomised to placebo or quetiapine (n=362, 42% completed). No significant change in heavy drinking or Clinical Global Impressions at 12 weeks.

35 Mania Depression Improvements in cocaine craving with both drugs Changes in mood not significantly associated with cocaine use Risperidone: mg/d Quetiapine: mg/d No placebo group

36 Challenges in assessing treatment effects Small number of studies overall e.g. No controlled trials of nicotine cessation for smokers with bipolar disorder available Most studies available are case studies or open label trials studying small numbers of patients with relatively short follow-up Very few well powered RCT s investigating treatment effects in co-morbid patients

37 Summary 1 Rates of alcohol and drug dependence much higher in bipolar disorder and also elevated in MDD BP2 and manic symptoms are risk factors for developing drug and alcohol abuse and dependence Co-morbidity impacts on clinical outcomes: increased risk of suicide, slower recovery and higher rates of admissions

38 Summary 2 Co-morbidity may be mediated by the dopamine-reward system or by impaired GABA function Mood stabilisers and antipsychotics may be effective in treating co-morbid addictions although evidence base is poor

39 Clinical implications 1 Look carefully for a history of co-morbid drug and alcohol dependence in patients with mood disorders (particularly BD) and vice versa Educating patients that they are at increased risk for substance dependence and the role that drug and alcohol use has in worsening outcomes in bipolar disorder is important

40 Clinical implications 2 Treat mood episodes as recommended in guidelines e.g. NICE, BAP however assess contribution of substance misuse to hypomania or mania in BD and consider if medically assisted withdrawal is required Review pharmacotherapy for bipolar disorder particularly if only on lithium, and consider adding sodium valproate.

41 Acknowlegments Allan Young (Centre for Affective Disorders, Kings College London) Anne Lingford Hughes (Centre for Neuropsychopharmacology, Imperial College London) David Nutt (Centre for Neuropsychopharmacology, Imperial College London)

42 BRITISH ASSOCIATION FOR PSYCHOPHARMACOLOGY 40 th Anniversary Summer Meeting July 2014 Cambridge Online CPD Resource Schizophrenia Substance misuse including comorbidity Bipolar disorder Perinatal disorders ADHD focussing on adults Depression Anxiety disorders Sleep Old Age Child and Adolescent (coming soon)

43 THANK YOU Dr. Paul Stokes Centre for Affective Disorders, Department of Psychological Medicine Institute of Psychiatry at King's College London Main Building, 4th floor, Room M , De Crespigny Park London SE5 8AF Tel: +44-(0)20 Click to edit 7848 Master 5088 subtitle style