When not to prescribe Benzodiazepines Youre getting nervous already, - PDF document

APNA 30th Annual Conference Session 2025: October 20, 2016 When not to prescribe Benzodiazepines… You’re getting nervous already, aren’t you? Alan “Tony” Amberg, MS MSN APN PMHNP ‐ BC Northwestern Memorial Hospital (Chicago) Lauren Prasek, MSN APN PMHNP ‐ BC Ronald Reagan UCLA Medical Center (Los Angeles) Objectives • After instruction, the learner will be able to: • Identify common benzodiazepines and describe their mechanism of action • Describe common uses vs. indicated uses for benzodiazepines (including misuses) and side/adverse effects associated with benzodiazepine use medications Recognize appropriate uses of and alternatives to benzodiazepines • Recognize appropriate uses of and alternatives to benzodiazepines Amberg 1

APNA 30th Annual Conference Session 2025: October 20, 2016 A national addiction? • 2008, Netherlands (pop. 16.3 million) ‐ >10m Rxs for benzos to 1.8 m individuals • 2009 stopped reimbursing for PCP Rxs of these meds • Kollen et al (2012) studied the impact in 2009 and 2010 • Short ‐ term users slightly reduced # of days of Rx episode • Long ‐ term users used as much, however, absolute # decreased 2.3% A national addiction on both sides of the ocean? • 2015: First US national prescription epidemiology study, used 2008 sample to estimate 75 million Rxs • However, national rate of use for age 65 ‐ 80 Men (6.1%) and Women (10.8%) despite many warnings about use in elderly – mostly from non ‐ psychiatrist providers • Highest rate of use (11.9%) observed among 80 ‐ year ‐ old women (Olfson, King, & Schoenbaum, 2015) More fun benzo facts • In all age groups, roughly 1/4 of pts receiving benzodiazepines involved long ‐ acting agents • Mean tx episode ranged from 224.9 days in young adults to 245.4 days in elderly • Across all age and sex groups <10% were getting Rx from a psychiatrist, esp. 65 ‐ 80 year olds (3.6%) (Olfson, King, & Schoenbaum, 2015) Amberg 2

APNA 30th Annual Conference Session 2025: October 20, 2016 GABA ( γ‐ amino butyric acid) Mechanism of action – Benzos, Barbiturates, etc. GABA ‐ A ionotropic receptor/ligand ‐ gated ion channel Five unit receptor (2 α units, 2 β units & 1 γ unit) with central chloride channel Modulates: • Chloride ions inhibit neural action potentials (Na & K) • Sedation • Seizure • Anxiety • Spasm • Perception of pain Other GABA receptors • GABA ‐ B G ‐ protein receptors to K channels • (Baclofen, GHB) • GABA αδ voltage dependent calcium channel receptors • Gabapentin, Pregabalin Modifying GABA receptors – old as civilization? • Alcohol “v 1.0”– also hits Opioid and Cannabinoid receptors • Barbiturates “v 2.0” (1864 – Adolf v Baeyer, 1904 1 st marketed) • High abuse/overdose potential (think Marilyn Monroe & Elvis Presley) • Now for anesthesia induction or seizure • Benzodiazepines “v 3.0” (1955 – Chlordiazepoxide or Librium, with Diazepam following in 1963) • …and then “Z ‐ drugs”, anti ‐ spasmodics, neuropathic pain… 9,000-Year-Old Beer Re-Created From Chinese Recipe John Roach for National Geographic News July 18, 2005 Amberg 3

APNA 30th Annual Conference Session 2025: October 20, 2016 Common Benzos • Alprazolam (short) 6 ‐ 12 hr half ‐ • Lorazepam (intermediate) 10 ‐ 20 life/high ‐ potency hrs/high potency • Chlordiazepoxide (long ‐ acting) 30 ‐ • Midazolam (short) 1.8 ‐ 6 200 hr/low potency hrs/twilight sedation • Clonazepam (intermediate)hrs/high potency • Diazepam (long ‐ acting) 30 ‐ 100 hrs/low potency • Diazepam metabolites Chlorazepate 30 ‐ 200 hrs • Oxazepam (short) 5 ‐ 15 hrs • Temazepam (intermediate) ‐ 22 hrs This is not new information “…there is no good evidence for their long term efficacy in the treatment of anxiety and insomnia…” “Adversely effects such as oversedation, tremor, ataxia and confusion are much more common in elderly patients. Ever since the benzodiazepines were first marketed 20 years ago their use has increased rapidly, and it is now estimated that between 12 and 16% of the adult population in developed countries use tranquillisers at some time each year.” (Lader & Petursson, 1983) This is not new information “Adverse effects include psychomotor impairment, especially in the elderly, and occasionally paradoxical excitement. With long term use, tolerance, dependence and withdrawal effects can become major disadvantages. Unwanted effects can largely be prevented by keeping dosages minimal and courses short (ideally 4 weeks maximum), and by careful patient selection.” (Ashton, H., 1994) Amberg 4

APNA 30th Annual Conference Session 2025: October 20, 2016 Indicated Uses General Psychiatric • Alcohol or drug ‐ induced Seizures • Sedation Induction • Anxiety (acute) • Seizure Prophylaxis & Treatment • Agitation (in some circumstances) • Muscle Spasm • Catatonia • Generalized Anxiety Disorder (GAD) • Anesthesia • Insomnia (acute and sparingly) Induction/Maintenance • Involuntary Movement Disorders • Tetanus • Panic Attacks (as a bridge only) Short ‐ term use only (2 to 4 weeks)! Common Misuses • ANYTHING over 4 weeks • Delirium (which is around ½ of general inpatient agitation cases) • Geriatric (see Beers Criteria) • GAD (indicated, but don’t do it) • Insomnia • PTSD (doesn’t work…really!) • Panic Attacks Adverse Effects 90 80 70 60 50 40 30 20 10 0 Respiratory Memory Menstrual Dysarthia Dizziness Drowsiness Depression Impairment Irregularity Alprazolam Diazepam Clonazepam Lorazepam Tannenbaum, C., Martin, P., Tamblyn, R., Benedetti, A., & Ahmed, S. (2014) Amberg 5

APNA 30th Annual Conference Session 2025: October 20, 2016 Alprazolam= Addictive • High potency: 1 mg Alprazolam = 20 mg Diazepam • Short to Intermediate half ‐ life 6 ‐ 12 hrs ‐ If given for sleep, there may be a hangover • Quick onset/Abrupt termination – like a light switch so every 12 hrs your patient will want more • Unique mechanism of action: Triazolo – ring structure= unique properties ‐ antidepressant and antipanic ‐ may cause mood cycling in Bipolar (mania) • Mood disinhibition may emerge in Alprazolam • (Keltner & Folks, 2005) Benzo Withdrawal Symptoms Psychiatric Effects Physiologic Effects • Depression • Autonomic Instability • Insomnia • Gastrointestinal • Irritability • Musculoskeletal • Rebound Anxiety • Neurologic • Tolerance Benzodiazepine Use Disorder Treatment • Prevention! ‐ Stick to the guidelines 2 ‐ 4 weeks use only and as a bridge to longer acting non ‐ dependence forming agents (Ashton, H. 2005) • Taper dose by 25% q 2 ‐ 3 weeks. Determine if the patient needs a longer acting or low potency alternative. Substitute with Diazepam – also consider Pregabalin • Let patients guide the taper – do not pressure the patient • (Ashton, C.H. 2013) • CBT has moderate evidence of efficacy with benzo taper at 3 months (Cochrane, 2015) • A Spanish study showed that training the PCPs in dose reduction with either written information or face ‐ to ‐ face follow produced 45% discontinuation at 12 mos vs 15% with TAU. (Vicens, Bejarano et al, 2014) Amberg 6

APNA 30th Annual Conference Session 2025: October 20, 2016 Reminder… In the elderly In individuals with Schizophrenia Antipsychotic, antidepressant and • Impairment to cognitive function benzodiazepine polypharmacy – • Risk of falls • MVA • aggressive and impulsive behavior • 283% suicidal deaths and 60% • Increased risk of dependence non ‐ suicidal deaths • Increased risk of dementia and death • Unfortunately, too often given (Olfson, King, & Schoenbaum, 2015) long term, so when you see a psych patient… Less is more…. (Tiihonen, J et al, 2012) Less is more…. Common Uses & Alternatives Common Responses to… Non ‐ pharmacologic Responses… Anxiety Attention to environment Psychotherapy – e.g. CBT Disorders Exercise Yoga/Relaxation Training Mindfulness ‐ Based Stress What is usually used? Reduction Alprazolam/Clonazepam Emotional response to illness Lorazepam/Diazepam Family needs Financial implications What are the alternatives? Addressing adequate sleep Nutrition SSRIs/SNRIs Endocrine Buspirone (Buspar) Common Uses & Alternatives Common Responses to… Preferred Responses… Insomnia Attention to environment Attention to patient/family What is usually used? emotional state Alprazolam/Clonazepam/ Delirium? Lorazepam Possible low dose antipsychotics Z ‐ drugs (Ambien, Lunesta, Sonata) No benzos or anticholinergics Low ‐ dose Quetiapine (Seroquel) Melatonin Agonists Hypnotic Antidepressants What is often ignored in the Alpha 2 agonists/Alpha 1 environment? antagonists No definite light/dark cycle Remove medications that disturb Disturbances in sleep sleep architecture LIKE EtOH or most benzos Lack of ambulation Failing to address patient anxiety Amberg 7