Re-evaluating the Use of Benzodiazepines A Quick Reference Guide [ Provider ] VA PBM Academic Detailing Service Real Provider Resources Real Patient Results Your Partner in Enhancing Veteran Health Outcomes VA PBM Academic Detailing Service Email Group: [email protected] VA PBM Academic Detailing Service SharePoint Site: https://vaww.portal2.va.gov/sites/ad Table of Contents Tips for Benzodiazepine Withdrawal . 1–2. Benzodiazepine Equivalent Doses and Example Taper . 3–4. Potential Medication Augmentation Strategies for Benzodiazepine Withdrawal . 5–6 Key Features of Anxiety and Trauma Related Disorders . 7. Management of Anxiety and Trauma Related Disorders . 8–16. Potential Contributors to Insomnia . 17. Management of Insomnia . 18–26 i Treatment for Behavioral and Psychological Symptoms of Dementia . .27–35 References . .36 . ii Discussing Benzodiazepine Withdrawal1–6 1. Assess patient’s willingness to discontinue or reduce the dose of benzodiazepine • Explore and acknowledge perceived benefits and harms and allow Veteran to express his/her concerns • Explain the risks of continued use (disinhibition, ineffectiveness, loss of mental acuity) and the benefits Tips for Benzodiazepine Withdrawal of stopping Figure 18. • If previous attempts haveStructure been made of a without Brief Educational success, explain Intervention that it is worth64 trying again 1 2. Agree on timing and discuss the symptoms likely to occur from withdrawal5 • Patients may experience withdrawal after >4 weeks of benzodiazepine use • Timeline of withdrawal: occurs within 1–7 days and can last 4–14 days (short vs . long half‑life, respectively) Benzodiazepine Withdrawal Symptoms5 Psychological Physical • Anxiety/irritability • Stiffness • Insomnia/nightmares • Weakness • Depersonalization • Gastrointestinal disturbance • Decreased memory and concentration • Flu like symptoms • Delusion and hallucinations • Paresthesia • Depression • Visual disturbances • Seizures 2 3. Provide written instructions for a structured medication taper. Be prepared to slow the taper if the patient reports significant withdrawal symptoms Benzodiazepine Equivalent Doses1–3,5 Chlordiazepoxide Diazepam Clonazepam Lorazepam Alprazolam Temazepam Approximate 25 mg 10 mg 1 mg 2 mg 1 mg 15 mg Benzodiazepine Equivalent Doses and Example Taper Dosage Equivalents Elimination >100 hr >100 hr 20–50 hr 10–20 hr 12–15 hr 10–20 hr Half-life* Benzodiazepine example dosage reduction and/or discontinuation**: • Switching to a longer acting benzodiazepine may be considered if clinically appropriate+ • Reduce dose by 50% the first 4 weeks, maintain on that dose for 1–2 months, then reduce dose by 25% every 2 weeks *Includes active metabolites; **these are suggestions only and a slower taper may be used (e .g . 10–25% every 4 weeks); +high dose alprazolam may not have complete cross tolerance, a gradual switch to clonazepam or diazepam before taper may be appropriate; in geriatric patients consider tapering the short acting agent until withdrawal symptoms are seen then switch to a longer acting agent; other treatment modalities (e .g . antidepressants for anxiety) should be considered if clinically appropriate . 3 Benzodiazepine Example Taper1–3,5 Milestone Suggestions Example: Lorazepam 4 mg bid Convert to 40 mg diazepam daily Week 1: 35 mg/day Week 2: Decrease dose by 25% Week 2: 30 mg/ day (25% of initial dose) Week 3: 25 mg/day Week 4: Decrease dose by 25% Week 4: 20 mg/day (50% of initial dose) Weeks 5–8: Hold dose 1–2 months Weeks 5–8: Continue at 20 mg/day for 1 month Week 9: Decrease dose by 25% every two weeks Weeks 9–10: 15 mg/day Weeks 11–12: 10 mg/day Weeks 13–14: 5 mg/day Week 15: Discontinue These are suggestions only and a slower taper may be used (e .g . 10–25% every 4 weeks); in geriatric patients consider tapering the short acting agent until withdrawal symptoms are seen then switch to a longer acting agent; other treatment modalities (e .g . antidepressants for anxiety) should be considered if clinically appropriate . 4 Potential Medication Augmentation Strategies for Benzodiazepine Withdrawal* Medication Evidence Dosing Range Carbamazepine • Case series and small open label studies indicate that carbamazepine 200–800 mg/day Potential Medication Augmentation Strategies for 7,8 may be helpful for BZD withdrawal symptoms divided doses Benzodiazepine Withdrawal • Double blind placebo controlled study (n = 40; 4 week BZD taper) found trends towards carbamazepine superiority in reducing withdrawal symptoms; more pronounced if on >20 mg/day diazepam equivalents9 Melatonin • Double blind studies indicate that that CRM may improve subjective CRM 2 mg at bedtime sleep quality but provide conflicting information on improving discontinuation rates12,13 • Double blind studies have found no difference in withdrawal symptoms with the use of CRM compared to placebo14, 15 *Gradually tapering the benzodiazepine to minimized withdrawal symptoms is the preferred method of discontinuation or reduction of dose . BZD = benzodiazepine; CRM = controlled release melatonin Limited and conflicting evidence supports the use of adjuvant pharmacotherapy in decreasing the severity of benzodiazepine withdrawal. 5 continued Potential Medication Augmentation Strategies for Benzodiazepine Withdrawal* Medication Evidence Dosing Range Gabapentin • 2 positive case reports of rapid inpatient BZD taper using gabapentin 600–900 mg/day for withdrawal symptoms10,11 divided doses Pregabalin • Case reports and one observational non‑comparative study indicate 150–450 mg/day that pregabalin may reduce withdrawal symptoms16,17 (Mean = 300 mg/day) Adding non‑pharmacological interventions (e .g . CBT), self‑help instructions, and patient education increases discontinuation outcomes . *Gradually tapering the benzodiazepine to minimized withdrawal symptoms is the preferred method of discontinuation or reduction of dose . BZD = benzodiazepine; CRM = controlled release melatonin Limited and conflicting evidence supports the use of adjuvant pharmacotherapy in decreasing the severity of benzodiazepine withdrawal. 6 Key Features of Specific Anxiety and Trauma Related Disorders5,18 Disorder Key Features Generalized • Excessive irrational worries about multiple events or activities (e .g . school/work difficulties) Anxiety Disorder • Physical symptoms like hyperventilation, tachycardia, sweating, muscle tension Obsessive- • Obsessional recurrent thinking, urges, or images that cause marked anxiety or distress Compulsive • Compulsive repetitive behavior (e .g . hand washing) or mental acts (e .g . counting) that individual Key Features of Anxiety and Trauma Related Disorder feels driven to do to reduce anxiety evoked by obsessions Disorders • Recurrent unexpected panic attacks (e .g . severe anxiety, accompanied by physical sensations such as shortness of breath, palpitations, or nausea), in the absence of obvious psychological causes Panic Disorder or triggers • Persistent concern about additional panic attacks and/or maladaptive changes in behavior related to the attacks • Extreme unrealistic fear of social situations (e .g . public speaking, eating in public) in which there is Social Anxiety possible exposure to scrutiny by others Disorder • Avoidant behavior around feared situation • History of a traumatic life event (e .g . threatened death, serious injury, sexual violation), often occurring during combat, car accident, or violent crime Posttraumatic • Intrusive symptoms (distressing memories, dreams, flashbacks); emotional numbness or Stress Disorder detachment; avoidance of perceived similar situations; alterations in arousal and reactivity (e .g . irritable behavior, hypervigilance) 7 Management of Anxiety and Trauma Related Disorders5,19,20 Social Generalized Obsessive Panic Posttraumatic Anxiety Anxiety Disorder Compulsive Disorder Disorder Stress Disorder Disorder Non-drug CBT Exposure Therapy CBT CBT CPT Treatments Exposure Therapy CBT Exposure Prolonged Exposure Applied Relaxation Therapy EMDR First-line Medication SSRIs SSRIs SSRIs SSRIs SSRIs Management of Anxiety and Trauma Treatment Options SNRIs Clomipramine Venlafaxine Venlafaxine Venlafaxine Related Disorders Buspirone Mirtazapine Pregabalin Other Non- Hydroxyzine Mirtazapine Mirtazapine Gabapentin Mirtazapine Benzodiazepine Quetiapine Venlafaxine TCA Pregabalin TCA Medication Augmentation of SSRI: Propranolol* Nefazodone Treatment Options ‑ Antipsychotics Prazosin (limited by evidence ‑ Lamotrigine (nightmares) or side effects) ‑ Topiramate CBT = cognitive behavioral therapy; CPT = cognitive processing therapy; EMDR = eye movement desensitization and reprocessing; SSRI = selective serotonin reuptake inhibitor; SNRI = selective norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant; *performance anxiety only . Benzodiazepines may be used for short‑term emergency management of generalized anxiety and panic disorders and may be useful on an as needed basis for the management of social anxiety disorders . 8 Comparison Among Commonly Used Antidepressants for Anxiety and Trauma Related Disorders5,21 Drug Class Drug Anti–Chol Sedation GI Withdrawal Notes Interaction SSRI Citalopram* N May cause QT prolongation Escitalopram N Sertraline N,D Paroxetine N Dosed at bedtime; weight gain Fluoxetine N No need to taper with discontinuation SNRI Venlafaxine N May increase blood pressure at high doses Duloxetine N Monitor liver function TCA Amitriptyline C Dosed at bedtime; postural hypotension; weight gain; Imipramine C overdose can cause seizures,