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Treating Anxiety in the

Substance Use Disordered Patient August 26, 2015

Stephen A. Wyatt, D.O.

Med. Dir., Addiction Medicine Carolina HealthCare System

Charlotte, NC

No Financial Disclosures

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Target Audience

• The overarching goal of PCSS-O is to offer evidence-based trainings on the safe and effective prescribing of opioid medications in the treatment of pain and/or opioid addiction.

• Our focus is to reach providers and/or providers-in-training from diverse healthcare professions including physicians, nurses, dentists, physician assistants, pharmacists, and program administrators.

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Educational Objectives

• At the conclusion of this activity participants should be able to: have an understanding of the difficulties in diagnosis and

treatment of anxiety in the substance use disordered population.

have a working understanding of other medications that can assist in treating anxiety in this population.

consider various psychotherapeutic interventions to reduce anxiety with or without concurrent medication.

understand ways to approach this often anxiety producing subject in order better engage the patient in considering discontinuing their use of benzodiazepines.

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Assessment of Anxiety

Thyroid disease Vestibular disorders Cardiac disease Respiratory disease Cancer Chronic pain

Mitral valve prolapse Irritable bowel syndrome Allergic conditions Migraine

General Medical Considerations

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Anxiety Disorders

• panic disorder, • post-traumatic stress disorder (PTSD), • social phobia (or social anxiety disorder), • specific phobias, • generalized anxiety disorder (GAD), • obsessive-compulsive disorder (OCD)

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Co-Morbidity with Anxiety

• Psychiatric symptoms need to be considered, however an evaluation for substance-induced disorders is important

• A different clinical course may be expected if psychiatric symptoms are substance induced. 85% or more of substance-induced symptoms improve

rapidly with abstinence Schuckit MA. Addiction, 2006, 101: 76-88.

• Generalized Anxiety Disorder with a concurrent SUD is associated with high overall vulnerability for additional psychopathology, e.g. externalization, higher disability and continued higher use of alcohol and drugs to relieve anxiety symptoms. Alegria AA, et.al., J Clin Psychiatry, 2010 71(9), 1187-95

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Anxiety Disorders in the

Substance Use Disorder Patient

• genetic predisposition to anxiety disorders as a precursor to an SUD.

• higher incidence of adverse childhood events. • social problems secondary to high risk behavior and

deviance. • neurobiology of the adaptation to alcohol and other

drugs resulting in anxiety seen in both intoxication and withdrawal.

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Management Acute Anxiety

• Anxiety can be adequately treated either Medication or Psychotherapy

• There is ample evidence the combination is most effective.

• Hyman SE, Scientific American® Medicine. 2000

• Abstinence of Alcohol and other Drugs

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Benzodiazepines

• “The most widely used tranquilizer in America is more addictive than Valium and is often less effective than nondrug treatments for anxiety”

Consumer Reports, January 1993

XANAX

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Treatment of Anxiety in the Vulnerable Population

• Intentional abusers of benzodiazepines usually have other substance abuse problems.

• Benzodiazepines are usually a secondary drug of abuse-used augment the high received from another drug to offset the adverse effects of other drugs.

• Specific drug use patterns To ease the "crash" from cocaine 29%-33% of alcohol abusers take BZs Up to 80% of opiate abusers have taken BZs

O’Brien C, J Clin Psychiatry 2005;66 (suppl 2) Benzodiazepine Dependence, Toxicity, and Abuse: Task force report, APA, 1990

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Treatment Admissions

• Number of benzodiazepine and opiate combination admissions: 2000 to 2010 Increased from 5,032 to 33,701

61.2 percent of benzodiazepine

and opiate combination admissions reported daily use of any substance compared with 34.6 percent of other admissions

SAMHSA Treatment Episode Data Set (TEDS), 2000 to 2010.

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Medication Management of Anxiety

• Non-benzodiazepine pharmaco-management is preferable in treating co-occurring depression in substance use disordered patients.

• Hazards of BDZ use potential dependence with prolonged use, potential for withdrawal syndromes rebound effects on abrupt discontinuation

• Disclaimer: Benzodiazepines may be useful adjunctively with other psychotropic medications to treat patients with very distressing or impairing symptoms. The benefit of more rapid response to

benzodiazepines balanced against troublesome side effects (e.g., sedation, cognition) and physiological dependence.

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Pharmacologic Management Acute Anxiety/PTSD

• Cochrane meta-analysis 2006, 35 short-term randomized controlled trials 17 of the trials, symptom severity was

significantly reduced in the medication groups relative to placebo. Evidence of efficacy for the SSRIs, across all

symptom clusters and for co-occurring depression.

Stein DJ, Cochrane Database Syst Rev 2006

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Pharmacotherapies – PTSD SSRIs

• Paroxitine Positive study – Marshall et. al. 2007

• Sertraline Positive study – Stein et.al. 2006

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Pharmacotherapies – PTSD SSRIs

Negative Trials – Combat Veterans • Sertraline vs. placebo combat veterans with PTSD 12 weeks of flexibly dosed sertraline (mean dosage =

156 mg/day) (n169) PTSD symptom reduction not significant both groups, combat-related PTSD associated with

poorer out- come compared with non-combat-related PTSD.

Friedman MJ,J Clin Psychiatry 2007; 68:711–720

• Similar results in an Isreali combat veteran trial, 2002 Zohar,J, J Clin Psychopharmacol 2002

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Pharmacotherapies – PTSD SSRIs

Positive Trials – Combat Veterans • Bosnian veterans Fluoxitine vs placebo

− 24 wk trial (n144) − Improvement in acute, depression, prevention

Martenyi F, Eur Neuro- psychopharmacol 2006

These veterans were younger and had been in combat more recently than previous trials

• SSRI remain first line medication in the treatment of PTSD Koen N; Dialogues in Clinical Neuroscience. 2011.

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Pharmacotherapies – PTSD

• Venlafaxine XR Improvement over placebo PTSD symptoms of

avoidance/numbing and reexperiencing, not hyperarousal. Davidson J, Arch Gen Psychia- try 2006; Venlafaxine vs Sertraline vs Placebo

− Venlafaxine statistically better than both Davidson J, J Clin Psychopharmacol 2006

• Bupropion XL vs placebo no differences in PTSD Becker ME, J Clin Psychopharmacol 2007

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Pharmacotherapies – PTSD

• Trazodone (5-HT2 antagonist and SSRI) Antidepressant, sleep and antianxiety Decrease benzodiazepine use

Frecska E, Neuropsychopharmacologia Hungarica. 2010

• Alpha adrenergic antagonists prazocin (3-15mg) used in treatment as usual including other

medications. − primary outcome sleep/nightmares significant

o improve total sleep time and REM − also showed improvement in PTSD − duplicate studies consistent

Raskind MA, Am J Psychiatry 2003; Raskind MA, Biol Psychiatry 2007; Taylor FB, Biol Psychiatry 2008

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Pharmacotherapies – GAD

SSRI in treatment of Generalized Anxiety Disorder (GAD) evidence-based guidelines recommend initial treatment with

either SSRI or SNRI Some selectivity in efficacy and the tolerability of treatment GAD with SSRIs or SNRIs should usually be continued for 6–12

months Comparative studies show superiority to placebo but not to one antidepressant over another.

Baldwin DS, Current Topics in Behavioral Neurosciences. 2010.

• Nefazodone vs placebo GAD significant improvement Davis LL, J Clin Psychopharmacol 2004

• Mirtazapine vs placebo

GAD significant improvement Davidson JR, Biol Psychiatry 2003

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• Buspirone reducing serotonin (5-HT) release as a partial agonist at

5-HT1A receptors and as a presynaptic full agonist comparable but slightly weaker efficacy than

benzodiazepines and a slower onset known to relieve the cognitive aspects of GAD questionable long-term efficacy

• Bupropion XL positive trial in comparison study with escitalopram

Alexander Bystritsky, et.al.Psychopharmacol Bull. 2008;41(1):1-9.

Pharmacotherapies – GAD

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Pharmacotherapies – GAD

• Tricyclic Antidepressants Kahn RJ, J Affect Disord 1987

Imipramine comparable to SSRIs Hoffman EJ. Mount Sinai J Med 2008

Doxepin comparable anxiolytic to diazepam

− Greater side effects d'Elia G, Acta Psychiatr Scand Suppl. 1974

Comparison Imipramine with Mirtazipine − Similar response in anxiety and sleep − some greater prolonged effect of imipramine on anxiety − mirtazipine greater improvement in depression

Moleman, P, Pharmcopsychiatry,1999

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Pharmacotherapies – Anxiety

• Clonidine (alpha 2 agonist) Superior to placebo in GAD and Panic D/O

Hoehn-Saric R, Arch Gen Psychiatry. 1981

Reduces symptoms of anxiety Giannini, AJ. Drugs of Abuse 1997

Hyperarousal in PTSD van der Kolk, BA. Journal of Affective Disorders 1987

Abuse potential Dennson SJ, Psychiatr Q. 2001

May be helpful in induction of sleep without effecting REM latency

• Beta blockers early after trauma Ineffective longterm

Pitman RK, Biol. Psychiatry, 2002

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Pharmacotherapies – Anxiety

• Atypical antipsychotics Risperidone vs placebo (n20 women)

significant in reduction of hyperarousal, intrusive Padala PR, Int Clin Psychopharmacol 2006; Reich DB, J Clin Psychiatry 2004

Reproduced showing equivocal results.

some evidence risperidone and olanzepine may augment sertraline Hamner MB, Int Clin Psychopharmacol 2003 Stein MB, Am J Psychiatry 2002

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Pharmacotherapies – Anxiety Symptoms

• Anticonvulsants Topiramate

− non significant except for re-experiencing symptoms.

Tucker P, J Clin Psychiatry 2007

Divalproate − no improvement

Davis LL, J Clin Psychopharmacol 2008

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Pharmacotherapies – Anxiety Symptoms

Gabapentin GABA agonist Less effect than SSRIs in placebo trials good side effect profile

Pande AC, J Clin Psychpharmacology, 1999 Pregabolin

Evidence of augmentation of SSRI, SNRI and combination Vitali M, J Clinical Psychopharm, 2013

Tiagabine (selective GABA reuptake inhibitor (SGRI).)

some efficacy in panic disorder mostly non significant but some mild early improvement that was sustained

Connor KM, Psychopharmacology (Berl) 2006

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Psychotherapeutic Management

• CBT Cognition

− Psycho-education Behavior

− breathing − relaxation training

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Psychotherapeutic Management

• Psychoeducational normalization of the response not life threatening somatic response to stress

− the fight or flight response importance of identifying the stressor and

cognitively determining the level of safety

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An approach to talking to patients about anxiety

• Avoid the word anxiety. • Instead talk about the stress response (SR). • Describe what is meant by the SR. • Describe the importance of the SR. • Describe how their SR might be used in a positive way,

normalizing the response.

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Psychotherapeutic Management

• Breathing recognition of exhalation as a relaxation state understanding the importance of avoiding hyperventilation

− review the physiology of breathing o drive to breathe is associated with levels of CO2

• chest pressure on blowing off CO2 o excess levels of O2 have detrimental effects

• electrolyte imbalance • vasoconstriction • numbness of highly vascularized areas. • localized cramping • fainting

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An approach to talking to patients about panic

• Talk to them about the importance of not panicking! • Cognitive restructuring • Talk them through the physiology hyperventilation or

their experience. SOB Numbness and tingling of mouth and fingers Upset stomach Chest heaviness Visual abnormalities Fainting

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Psychotherapeutic Management

• Relaxation through breathing progressive relaxation exercises meditation visualization

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Psychotherapeutic Management

• Exposure Therapy It is well established that exposure-based

behavior therapies are effective treatments for anxiety.

Torres AR, et al.. Psychiatr Serv. 2007;58:977-982. Foa EB, et al. J Consult Clin Psychol. 2005;73:953-964

Develop an exposure hierarchy − Subjective Units of Discomfort

Gradual systematic exposure Elimination of safety behaviors Cognitive restructuring

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Psychotherapeutic Management

• Exposure Therapy Re-exposure

− imagining − in vivo − directed therapeutic − written − verbal − taped narrative

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Psychotherapeutic Management

• Brief exposure therapy single episode exposure-based behavioral

therapy intensity of stimuli adjusted to patient’s comfort

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Psychotherapeutic Management

• Eye Movement Desensitization and Reprocessing (EMDR) with or without CBT typically this is done following a prolonged period

of CBT so the patient has some skill in self relaxation. evidence of improvement of PTSD, depression,

dissociative symptoms.

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Promote Healthy Behaviors

• Promote healthy behaviors exercise; sleep hygiene; decreased use of caffeine, tobacco, alcohol, and

other potentially deleterious substances.

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Summary

• Make an appropriate diagnosis • Reduce towards discontinuation all alcohol and illicit

drug use. • Consider medication management along with

psychotherapy and encouragement of a healthy lifestyle.

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PCSS-O Colleague Support Program

• PCSS-O Colleague Support Program is designed to offer general information to health professionals seeking guidance in their clinical practice in prescribing opioid medications.

• PCSS-O Mentors comprise a national network of trained providers with expertise in addiction medicine/psychiatry and pain management.

• Our mentoring approach allows every mentor/mentee relationship to be unique and catered to the specific needs of both parties.

• The mentoring program is available at no cost to providers.

• Listserv: A resource that provides an “Expert of the Month” who will answer questions about educational content that has been presented through PCSS-O project. To join email: pcss-o@aaap.org.

For more information on requesting or becoming a mentor visit: www.pcss-o.org/colleague-support

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PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with: Addiction Technology Transfer Center (ATTC), American Academy of Neurology (AAN), American Academy of Pain Medicine (AAPM), American Academy of Pediatrics (AAP), American College of Physicians (ACP),

American Dental Association (ADA), American Medical Association (AMA), American Osteopathic Academy of Addiction Medicine (AOAAM), American Psychiatric Association (APA), American Society for Pain

Management Nursing (ASPMN), International Nurses Society on Addictions (IntNSA), and Southeast Consortium for Substance Abuse Training (SECSAT).

For more information visit: www.pcss-o.org

For questions email: pcss-o@aaap.org

Twitter: @PCSSProjects

Funding for this initiative was made possible (in part) by Providers’ Clinical Support System for Opioid Therapies (grant no. 1H79TI025595) from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department

of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.