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Beyond Benzos: Tips for Managing Anxiety Diane C. Reis, MD, MPH IU Health Arnett [email protected] 8/12/2017 1 Disclosures No financial conflicts of interest to report. Objectives • Identify and utilize non-benzodiazepine shortacting anxiolytics in a clinical setting. • Select and utilize longer acting anxiolytics in a clinical setting. • Identify and apply appropriate uses for benzodiazepines. • Taper and discontinue benzodiazepines in a safe and tolerable manner. Anxiety • Sort of the psychological equivalent of pain • Disorders we are considering in this discussion: – Generalized Anxiety Disorder – Panic Disorder – Social Anxiety Disorder – Performance/situational anxiety – Unspecified Anxiety Disorder • Not included: OCD (has been broken out from anxiety disorders in DSM V), PTSD 8/12/2017 4 Dx: Generalized Anxiety Disorder • Excessive worry most of the time for at least 6 months about a variety of topics/problems • Worry is challenging to control • 3+ of the following physical or cognitive sx: – Edginess/restlessness – Tiring easily/fatigue – Impaired concentration – Irritability – Muscle aches/soreness (and often others…) – Poor sleep 8/12/2017 5 Dx: Generalized Anxiety Disorder • Symptoms cause impairment in function • Symptoms not better explained by another physical or mental disorder or substance 8/12/2017 6 Dx: Panic Disorder • Spontaneous and unexpected occurrence of panic attacks (at least 4 of 13 possible sx, rapid onset, peak within 10 minutes) • At least one month of persistent worry about another attack or consequences of the attack OR maladaptive behaviors related to the attack • Not better explained by another disorder or substance 8/12/2017 7 Dx: Social Anxiety Disorder • Fear/anxiety in specific social settings in which a person feels observed or scrutinized • Fear that anxiety will show and lead to rejection • Social interactions avoided or tolerated only with pain/distress • Sx disproportionate to situation • 6+ months duration & impairment • Not better explained by another disorder or substance 8/12/2017 8 Performance Anxiety • Subset of social anxiety disorder (specifier added to indicate this) • Generally related to specific situations such as public speaking or similar performances 8/12/2017 9 Dx: Unspecified Anxiety Disorder • Anxiety symptoms that are clearly out of the ordinary and impairing but don’t meet criteria for a more specific anxiety disorder • Not due to another disorder or substance 8/12/2017 10 Please remember: • These disorders are chronic – 3 days of anxiety is not a disorder! • First line treatment for anxiety disorders should include therapy (CBT does particularly well for these) and behavioral interventions (exercise, sleep hygiene, limit/eliminate caffeine) • Psychopharm interventions have significant overlap across these disorders 8/12/2017 11 First steps in treatment • SSRIs – Can cause a few days of initial worsening of anxiety; start low (half of minimum effective dose) – Take 3-6 weeks to see effect and it is unusual for a person to describe a sudden, strong effect – Takes up to 12 weeks to see the full effect of a given dose (patience, grasshopper) – Please note that paroxetine has multiple negatives studies in age <25, would avoid in this group 8/12/2017 12 First steps in treatment • SSRIs – My practice: try at least two before switching class – Selection based on metabolic interactions, drug half-life, side effects • Side note on bupropion: I see this used for anxiety; it is mildly stimulating and has poor evidence for use in anxiety, also if you’re using the SR formulation for anything, make sure you’re dosing AM and early PM (not HS!!!) 8/12/2017 13 Second line options • SNRIs – For some, the addition of the noradrenergic effect has a notable difference – Venafaxine note: minimal NE activity at doses below 150 daily of the XR formulation – Monitor BP, particularly if this has been a problem in the past – Can be difficult to discontinue, taper slowly and, if needed, give the patient a brief (3-7 day) course of fluoxetine to smooth the end of the taper 8/12/2017 14 Second line options • Mirtazapine 8/12/2017 – The good: sedating in most people and some earlier anxiolysis due to activity alpha2 and histamine receptors – The bad: increased appetite causing weight gain (though sometimes that’s a good thing) – Can be used first line if you have a patient who’s not sleeping or eating and you’re concerned about weight loss – Can be used to augment SSRIs/SNRIs – Note: after 15 mg a day, sedation does not increase 15 Other longer-term treatments • TCAs – Differing balances of serotonergic and noradrenergic activity – Anti-cholinergic, beware of use in elderly, and be aware of the related side effects – Usually at least somewhat sedating – HIGH LETHALITY IN OVERDOSE 8/12/2017 16 Shorter-acting anxiolytics • Buspirone – Generally takes at least a week for effect and up to a month for full effect – Dosed BID-TID – More effective at higher doses (30-60 mg/day) – Sometimes used PRN, very limited evidence (active placebo???) – Strongest evidence as augmentation strategy, not as monotherapy – Usually safe and well tolerated with very low potential for abuse 8/12/2017 17 Shorter-acting anxiolytics • Hydroxyzine – Dosed BID-TID, generally 25-50 mg/dose – Most sedating in the first 3 days – Best evidence is for use as a scheduled agent – Anti-cholinergic, avoid in elderly, consider if other anti-cholinergics present and overall burden (area of evolving research) – No withdrawal, generally easy to discontinue – Anxiolysis is fairly rapid though related to sedation 8/12/2017 18 Shorter-acting anxiolytics • Beta blockers – Propranolol, metoprolol, atenolol most commonly used – Low doses (propranolol 10 g, metoprolol 12.525 mg, atenolol 25 mg) – Strongest evidence for PRN use for performance-type situations: speeches, tests, musical performances – I use this at times for social anxiety as well – Take 30-60 minutes prior to event – Warn for sx of low BP, do trial dose at home 8/12/2017 19 Shorter-acting anxiolytics • Clonidine – Used off-label, limited clinical studies – Some evidence for managing irritability or mood instability in borderline personality disorder – Start 0.1 mg BID, I will often dose 0.1 mg BID scheduled plus 0.1 mg daily PRN (3 total doses) – Little or no abuse potential, fairly rapid effect 8/12/2017 20 Shorter-acting anxiolytics • Gabapentin – Usually used at lower doses (100-300 mg/dose) either scheduled or PRN up to TID – Off-label use, mimimal evidence base but ample anecdotal suggestion that this has some anxiolytic effect – Compared to benzos, quite limited abuse potential 8/12/2017 21 Benzodiazepines • Effective in the short term • Fail to separate from placebo after about 2 weeks of regular use • Physiologic dependence and addiction • Interaction with opiates • Cognitive, motor, judgment effects • Disinhibition and intoxication 8/12/2017 22 Benzodiazepines in practice • Consider duration of action and potential for withdrawal/discontinuation symptoms • Consider site of metabolism (hepatic vs renal) • Don’t start unless there’s a plan to stop! • Avoid as a first line agent – remember most anxiety disorders present in the chronic phase (“it’s a marathon, not a sprint”) • Know your own max doses and be willing to stick to them 8/12/2017 23 Commonly used benzos • Alprazolam (Xanax): effect 3-5 hrs, euphoria early in dose, abrupt discontinuation effect, highest abuse potential, ugly withdrawal • Lorazepam (Ativan): effect 5-8 hrs, renally metabolized, used as comparator for BZD equivalencies • Diazepam (Valium): effect 6-8 hrs plus active metabolites, stored in fat and can have unpredictable release • Clonazepam (Klonipin): effect 7-10 hours, “smoother” activity, generally 1:1 equivalence with alprazolam, usually my first choice 8/12/2017 24 A small rant on Xanax… • The “ideal” Xanax patient: severe anxiety/panic that emerges in rare circumstances (e.g. bad turbulence while flying) and resolves in a predictable period of time, otherwise good coping skills and function, probably uses this less than once a month • 2 mg “bars” have high street value • Once people have tried this, it’s really hard to get them to use something else (nothing else gets you high the same way!) • Interferes with therapy! 8/12/2017 25 My “max” doses • Alprazolam: I don’t start this and I push my patients to switch to a longer-acting agent • Lorazepam: 1-2 mg TID • Diazepam: 10 mg TID • Clonazepam 1 mg TID • Note: I do inherit patients on higher doses, next steps are very case-dependent • Note: I do not start regimens with multiple 8/12/2017 26 So what about chronic users? Stable Unstable Motivated Unmotivated 8/12/2017 27 Stable & motivated to taper • Continue treatment with long-term anxiolytic and/or therapy if applicable • If needed, convert to longer-acting agent • Taper total daily dose by 10-20% at a time, decreasing no more frequently than q1-2 weeks and ideally q1-2 months • May need to slow even further at the end of the taper 8/12/2017 28 Stable but not motivated to taper • Explore concerns about tapering – bad experiences in the past? Concerned that “this is the only thing that keeps me together”? • Psychoeducation: what is perceived as anxiety may be benzo withdrawal, little evidence for efficacy with long-term use, risk for interactions, future potential problems, cognitive sfx • Discuss expectations (“I know that this time of year is stressful but when I see you in March, expect that we will begin to very gently taper.”) 8/12/2017 29 Not stable but motivated to taper • Consider increasing other treatment or support – add therapy or increase frequency, plan behavioral interventions, enlist family/friends, substitute a non-benzo anxiolytic • Err on the side of smaller dose changes that are done less frequently and be willing to adjust to life circumstances • Reinforce positive changes that you are observing 8/12/2017 30 Not stable or motivated to taper • Establish clear treatment goals – what does “better” look like? • Create clear expectations, consider a signed contract • There are patients who will remain on high doses of benzos – pick your battles • Communication with other treating doctors is key • Motivational interviewing techniques 8/12/2017 31 Example 1 Mr. X is taking 2 mg of Xanax three times a day for his GAD but is doing pretty well and wants to wean off of this. He has been on this dose for 3 years. 1) Convert to a longer-acting agent (2 mg TID Xanax = 2 mg TID clonazepam) 2) Decrease total daily dose by 10-20% (e.g. 1.5 mg AM and HS, 2 mg PM or 2 mg AM and HS, 1 mg PM) 3) Continue to decrease by 1 mg a month until he is taking 1 mg TID, then decrease by 0.5 mg a month. 8/12/2017 32 Sample Schedule Month AM Dose PM Dose HS Dose 0 2 mg 2 mg 2 mg 1 2 mg 1 mg 2 mg 2 1 mg 1 mg 2 mg 3 1 mg 1 mg 1 mg 4 1 mg 0.5 mg 1 mg 5 0.5 mg 0.5 mg 1 mg 6 0.5 mg 0.5 mg 0.5 mg 7 0.5 mg 0.25 mg 0.5 mg 8 0.5 mg x 0.5 mg 9 0.25 mg x 0.5 mg 10 0.25 mg x 0.25 mg 8/12/2017 33 Example 1 Mr. X is taking 2 mg of Xanax three times a day for his GAD but is doing pretty well and wants to wean off of this. He has been on this dose for 3 years. • Consider adding regular exercise, meditation, scheduled enjoyable activities • Consider enlisting a friend or family member to act as a “cheerleader” • If symptoms begin to worsen, consider use of a non-BZD anxiolytic 8/12/2017 34