Substance Use Disorders

Substance Use Disorders
Evan Goulding, MD PhD Department of Psychiatry, Northwestern University 11/10/2016

Neurobiology - General Pharmacology - Specific
Lecture Covers Neurobiology - General Pharmacology - Specific Pharmacological Treatment Prescription drugs

Objectives Summarize major systems in SUDs
Understand different mechanisms of drugs Know basics of adverse drug effects Describe pharmacological treatment Practice safer prescribing

Neurobiology - General Neurobiology - Specific
Lecture Topic Neurobiology - General Neurobiology - Specific Pharmacological Treatment Prescription drugs

Why Do People Take Drugs?
To feel good To have novel - Feelings - Sensations To share experience To feel better Why would anyone abuse drugs? Research has shown that people generally take drugs to either feel good (i.e., sensation seekers or anyone wanting to experiment with feeling high or different) or to feel better (i.e., self-medicators or individuals who take drugs in an attempt to cope with difficult problems or situations, including stress, trauma, and symptoms of mental disorders). Images: courtesy of Vivian Felsen To lessen - Anxiety - Worries - Fears - Depression - Hopelessness

Natural Rewards and Dopamine DA Concentration (% Baseline)
Food Sex 200 200 NAc shell 150 150 DA Concentration (% Baseline) % of Basal DA Output 100 100 Empty 50 Natural rewards stimulate dopamine neurotransmission. Eating something that you enjoy or being stimulated sexually can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals. Its increase is shown in response to food or sex cues. This basic mechanism of controlled dopamine release and reuptake has been carefully shaped and calibrated by evolution to reward normal activities critical for our survival. Box Feeding Female Present 1 2 3 4 5 6 7 8 60 120 180 Sample Number Time (min) Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997. 6

Drugs and Dopamine COCAINE MORPHINE AMPHETAMINE ETHANOL 400 100 200
100 200 300 1 2 3 4 5 hr % of Basal Release % of Basal Release 100 150 200 250 1 2 3 4 5 hr 0.5 1.0 2.5 10 Dose mg/kg DA AMPHETAMINE ETHANOL 100 200 300 400 500 600 700 800 900 1000 1100 1 2 3 4 5 hr % of Basal Release DA 250 100 150 200 1 2 3 4hr % of Basal Release 0.25 0.5 2.5 Dose (g/kg ip) Nearly all drugs of abuse increase dopamine neurotransmission. This slide shows the increase in brain dopamine (DA) levels (measured in animals) following exposure to various drugs of abuse. All of the drugs depicted in this slide have different mechanisms of action, however they all increase activity in the brain reward pathway by increasing dopamine neurotransmission. It is because drugs activate these brain regionsusually more effectively and for longer periods of time than natural rewardsthat they have an inherent risk of being abused. Di Chiara and Imperato, PNAS, 1988

Ventral Tegmental Area
Dopamine and Reward Dopamine Neuron Ventral Tegmental Area (VTA) Nucleus Accumbens (NAc)

GABA Inhibitory Feedback
Dopamine and Reward Glutamate Excitatory Input Enkephalin Inhibitory Neuron Enkephalin or Dynorphin Inhibitory Neuron GABA GABA Inhibitory Feedback Dopamine Neuron Ventral Tegmental Area (VTA) Nucleus Accumbens (NAc) Dopamine Receptors GABA-A Receptors Presynaptic Opioid Receptors (m, d?) m Opioid k Opioid 5HT2C Serotonin Excitatory Input REWARD

Multiple Neurotransmitters
Dopamine Serotonin Glutamate γ-Aminobutyric Acid (GABA) Endorphins Endocannabinoids Norepinephrine Corticotropin-Releasing Factor (CRF) Neuropeptide Y (NPY)

Not Just VTA and NAc Breiter et al, Neuron 1997 Rush
AC – R Anterior Cingulate Cau – Cuadate Put – Putamen BF – L Basal Forebrain I – R Insula VT – Ventral Tegmentum pThal – Posterior Thalamus pHip – Left Posterior Hippocampus PC – R Posterior Cingulate Craving Nac – Nucleus Accumbens Amy – Left Amygdala Pahip – Right Parahippocampal Gyrus Breiter et al, Neuron 1997

Multiple Neural Systems
PFC – prefrontal cortex OFC – orbital frontal cortex Nac- nucleus accumbens ACC – anterior cingulate cortex SCC – subcallosal cingulate cortex VP – ventral pallidum Thallamus also involved Insula also involved (insula represents the interoceptive effects of drug taking, making this information available to conscious awareness, memory and executive functions) Nac/VP: Reward/Salience Expected reward Error signal Addiction disrupts salience PFC/ACC: Inhibition Integrate information Select appropriate behavior Inhibitory control Hypoactive in addiction OFC/SCC: Motivation/Drive Establish priorities Establish motivation Hyperactive craving, hypoactive withdrawal Amygadala/Hippocampus: Memory Relate cues to experience Habit Rapid selection, immediate need (fight/flight) Reward perceived emotional need

Multiple Neural Systems
Control Reward Drive GO STOP Memory

Not just using alcohol/drugs Compulsive seeking and taking Loss of control in limiting use Risky, harmful use, problems Usually after prolonged use 14

Alterations → Disorder
Control GO Drive Reward STOP Decades of research have revealed addiction to be a disease that alters the brain. We now know that while the initial decision to use drugs is voluntary, drug addiction is a disease of the brain that compels a person to become singularly obsessed with obtaining and abusing drugs despite their many adverse health and life consequences. Memory

Neuronal Dendrites in the Nucleus Accumbens
Drugs Change the Brain Neuronal Dendrites in the Nucleus Accumbens Exposure to some drugs of abuse can change the structure of neurons in the brain. Stimulants like amphetamines can alter the structure of neurons. In this case, the dendrites of dopamine neurons in the nucleus accumbens—a part of the reward pathway—have more dendritic spines or connections in the amphetamine exposed animal compared to one treated only with saline. Saline Amphetamine Robinson & Kolb, Journal of Neuroscience, Volume: 1997

DA D2 Receptor Availability Dopamine D2 Receptors Decreased
Drugs Change the Brain Control Disorder DA D2 Receptor Availability Dopamine D2 Receptors Decreased Cocaine Meth Repeated drug exposure also changes brain function. Positron emission tomography (PET) images show similar changes in brain dopamine receptors resulting from addiction to different substances. Dopamine D2 receptors are one of five types of receptors that bind dopamine in the brain. The brain images on the left are those of controls, while those on the right are from individuals addicted to cocaine, methamphetamine, alcohol, or heroin. The striatum (which contains the reward and motor circuitry) shows up as bright red and yellow in the controls (in the left column), indicating numerous D2 receptors. Conversely, the brains of addicted individuals (in the right column) show a less intense signal, indicating lower levels of D2 receptors. This reduction likely stems from repeated over-stimulation of the dopamine receptors. Brain adaptations such as this contribute to the compulsion to abuse drugs. Alcohol Heroin

Methamphetamine Abuser
Drugs Change the Brain ↓ DAT 7 8 9 10 11 12 13 1.0 1.2 1.4 1.6 1.8 2.0 Time Gait (seconds) 4 6 14 16 Delayed Recall (words remembered) Dopamine Transporter Bmax/Kd Motor Task ↓ transporters ↓ motor reactions Memory Task ↓ memory Normal Control Another example: Methamphetamine abuse decreases dopamine transporter activity and compromises mental function. The brain image at the top left is a PET image from a normal control subject. The striatum is brightly lit in red and yellow, indicating the presence of many dopamine transporters, which contrasts with the brain of a methamphetamine abuser (bottom left). What does this mean functionally? The graphs on the right show the relationship between performance on a motor (upper right) and a memory task (lower right) and methamphetamine-driven decreases in dopamine transporters. The magnitude of the decline in the dopamine transporter binding is positively correlated with the extent of motor and memory impairment; thus the greater the decline, the greater the impairment in memory and motor reaction time. Methamphetamine Abuser Volkow et al., Am. J. Psychiatry, 2001.

Brain Changes Reverse Control Dopamine Transporter (DAT)
Methamphetamine DAT, 1 mo detox It takes time, but the brain can recover. This slide shows images of dopamine transporter (DAT) binding in three brains: (1) a healthy control (top); (2) a methamphetamine abuser one month after discontinuing drug abuse (middle); and (3) a methamphetamine abuser after 14 months of abstinence (bottom). The control brain shows a robust concentration of dopamine transporters in the striatum (red and yellow), while the methamphetamine abuser has a dramatic drop in DAT binding, even a month after drug abuse has stopped. Sustained abstinence, however, allows a near-full return of DAT binding to normal levels. Still, some of the behavioral effects of methamphetamine do not completely return to normal (not shown). This means that it can take a long time to recover from methamphetamine abuse, but recovery is possible. Methamphetamine DAT, 14 mo detox Volkow et al., J. Neuroscience, 2001.

Brain Differences Preexist
↑ DA receptor ↓ DA receptor The level of dopamine receptors in a person’s brain can influence whether they “like or dislike” the effects of a particular drug. Because dopamine is involved in the rewarding effects of drugs of abuse, it was hypothesized in this study that normal variation in the of number of dopamine receptors in a person’s brain could influence their response to drug exposure. To test this, human subjects were given the stimulant methylphenidate (Ritalin), their brains’ were imaged using PET, and they were asked whether they liked or disliked the drug’s effects. Those subjects who had high levels of dopamine receptors found the experience unpleasant, while those with lower levels of dopamine found it more pleasurable. This suggests that individual differences in a marker of dopamine function can influence an person’s susceptibility to continued drug Adapted from Volkow et al., Am. J. Psychiatry, 1999.

Brain diseases Characterized by Compulsive behavior Continued use despite negative consequences Changes in brain structure and function Preventable Treatable

Neurobiology - General Pharmacology - Specific
Lecture Topic Neurobiology - General Pharmacology - Specific Pharmacological Treatment Prescription drugs

Substances to Cover Alcohol and other sedatives Cannabinoids
Psychostimulants and derivatives Hallucinogens Opioids

Alcohol: Mechanisms of Action
Direct effects ↑ GABA-A receptor activation ↓ NMDA glutamate receptor activation ↓ Adenosine transporter function 5HT3R, nAchR, Ca/K channels Indirect effects ↑ Dopamine ↑ β-endorphins γ-Aminobutyric acid – GABA N-Methyl-D-aspartic acid - NMDA 5HT3R – potentiate nAchR – potentiate or inhibit BK – potentiate Ca – inhibit Caffeine reversibly block the action of adenosine on its receptor, which blocks the onset of drowsiness induced by adenosine

Alcohol: Adverse Effects
Depression - Common - Resolves in 1 month in 50% with abstinence alone Mild-moderate deficits cognition - In 60% with alcohol dependence - Abstraction, problem solving, learning and memory - Rapid recovery first month, more in first year WE – thiamine deficiency, emergency, triad of occulomotor abnormalities, cerebellar dsyfunction, altered mental state (opthalmoplegia, ataxia, confusion), variable severity not all symptoms of triad always present but minimum of 2 for diagnosis WKS – profound memory impairment, may follow WE, confabulation, spectrum of pathological, neurological, cognitive impairment following thiamine deficiency Several mechanisms through which chronic heavy alcohol intake may contribute to thiamine deficiency. The most important of these mechanisms include: -Inadequate nutritional intake -Decreased absorption thiamine from gastrointestinal tract, reduced uptake into cells -Impaired utilization thiamine in cells. ~50% AUD adults show some problems: Spatial skills Planning Learning and memory IQ and language OK Recovery Much in 1st month More in 1st year if sober More significant deficits - Wernicke’s encephalopathy – acute, symptom triad - Wernicke-Korsakoff syndrome – profound ↓ memory - Alcohol-related dementia

Sedative Hypnotics/Anxiolytics
Benzodiazepines (BZDs) - Alprazolam (Xanax) - Lorazepam (Ativan) - Clonazepam (Klonopin) - Diazepam (Valium) Z-drugs - Zolpidem (Ambien) - Zaleplon (Sonata) - Ezopiclone (Lunesta) Z-drugs GABA-A receptor modulators

Z-drugs BZDs: Abuse Liability ↑ Bioavailability → ↑ SUD
- Rapid rate of absorption - High lipophilicity ↑ Potency → ↑ SUD ↓ Half-life → ↑ SUD Z-drugs - Zolpidem (Ambien) - Zaleplon (Sonata) - Ezopiclone (Lunesta) BZDs > Z-Drugs

Benzodiazepines Potency Half-Life Lorazepam (Ativan)
High (0.5-1 mg) Low (10-20 mg) Half-Life Short (<24 hrs) Lorazepam (Ativan) Alprazolam (Xanax) Triazolam (Halcion) Temazepam (Restoril) Long (>24 hrs) Clonazepam (Klonopin) Diazepam (Valium) Chlordiazepoxide (Librium) GABA-A modulators

BZDs: Adverse Effects Motor impairment Cognitive impairment
- ↓ Driving skills → ↑ accidents - ↑ Falls → ↑ hip/femur fractures (> 65 yo) - Z-Drugs < BZDs Cognitive impairment - Impaired recall new information, “blackouts” - Sedation → impairs work, ↑ accidents - Zolpidem (Ambien) ≈ BZDs - Zopiclone (~Lunesta) < BZDs

γ-Hydroxybutyrate (GHB)
Similar GABA Synthesized endogenously Low affinity GABA-B receptor High affinity GABA-A subtype Possible other receptors Steep dose response curve Overdose risk 15mg/kg somnolence 30mg/kg loss of consciousness, coma Withdrawal can be like alcohol or benzos ie life-threatening

Marijuana = Natural Cannabinoids
Comes from the plant Cannabis sativa Composed of > 500 compounds 66 compounds are "cannabinoids” Caps for title?

Cannabinoids Psychoactive Tetrahydrocannabinol (THC) – partial agonist
Cannabinol (CBN) Cannabinodiol (CBDL) Non-psychoactive Cannabigerol (CBG) Cannabichromene (CBC) Cannabidiol (CBD) - antagonist

Endocannabinoids CB1 receptor CB2 receptor Endogenous Ligands
Psychoactive effects Brain and spinal cord (CNS) THC = partial agonist (positive effect) CBD = antagonist (blocker of CB1) CB2 receptor Immune cells Immune function and inflammation Endogenous Ligands Anadamide (AEA) 2-Arachidonoylglycerol (2-AG) Arachidonate-based lipids N-arachidonoylethanolamide, AEA 2-arachidonoylglycerol, 2-AG

Marijuana: Adverse Effects
Confidence Development of cannabis use disorder High Motor vehicle accidents (MVA) Symptoms of chronic bronchitis Diminished lifetime achievement Progression to other drug use Medium Schizophrenia Depression or anxiety Abnormal brain development Lung cancer Low Use in adolesence – impaired neural connectivity, significant small effect IQ (decline with duration use) Adverse Health Effects of Marijuana Use Nora D. Volkow, M.D., Ruben D. Baler, Ph.D., Wilson M. Compton, M.D., and Susan R.B. Weiss, Ph.D. N Engl J Med 2014;370:

Cannabinoids: Disorder Risk
Try cannabis use % Start use as teenager % Smoke daily %

Cannabinoids: MVA Risk
↑ 2 fold with recent cannabis use ↑ 5 fold 0.08% blood alcohol level ≥ 2 ng/ml impaired driving ≥ 1 ng/ml 3-7 x more likely responsible Synergistic increase with combined use detectable ≥ 1 ng/ml (and especially above) 3-7 x more likely responsible accident than non-intoxicated

Synthetic Cannabinoids
FDA approved compounds - Dronabinol (Marinol) - Nabilone (Cesamet) Research compounds Most > potency than THC Full agonists at the CB1 receptor JWH18

Recreational use of synthetic cannabinoids Labeled “not for human use”
Spice: Marketing Recreational use of synthetic cannabinoids Sold as herbal incense Labeled “not for human use” Spice Red magic K Red dragon Diesel Serenity

Synthetic Cannabinoids
SC are commonly used - 11% 12th graders in 2012 - Easy to obtain despite ban - Not detected on standard urine toxicology - Risks not well known Ask about use Tell patients about possible risks - ↑ Anxiety - ↑ Psychosis

Marijuana vs Synthetic Cannabinoids
Nature controls dose Low-medium potency Partial CB1 agonist Contains CBD No dose control High potency Full CB1 agonist No CBD

Stimulants Cocaine Amphetamine ↓ Dopamine reuptake Metabolizes rapidly
Effects last 1-2 hours Amphetamine ↓ Dopamine reuptake ↑ Dopamine release Metabolizes slowly Effects last hrs

Methylenedioxyamphetamine Methylenedioxymethamphetamine
Molly and Bath Salts MDA Methylenedioxyamphetamine MDMA, Ecstasy/Moly Methylenedioxymethamphetamine

Molly and Bath Salts MDA, Ecstasy/Molly Methylenedioxyamphetamine MDMA, Ecstasy/Molly Methylenedioxymethamphetamine Mescaline

Molly and Bath Salts MDA, Ecstasy/Molly Methylenedioxyamphetamine MDMA, Ecstasy/Moly Methylenedioxymethamphetamine Mescaline

Stimulants: Mechanisms
Direct effects ↑ Dopamine, block/release transporter ↑ Serotonin, block/release transporter ↑ Norepinephrine, block/release transporter - ↓ nAchR activation Indirect effects ↑ Glutamate ↑ β-endorphins

Mood elevation Increased energy Enhanced sociability Sexual arousal
Stimulants: Effects Users most desirable effects: Mood elevation Increased energy Enhanced sociability Sexual arousal Washton, A.M. & Tatarsky, A. NIDA research monograph

Stimulants: Adverse Affects
Visual motor skills Attention Verbal memory Inhibitory control Risk-reward decision making Amphetamines → persistent psychosis

Hallucinogens: Serotonergic
LSD Acid, blotter, microdot Psilocybin Magic mushrooms, shrooms Mescaline Peyote, mescal, buttons Caveat – like most other drugs of abuse likely activate other systems

Hallucinogens: LSD Most common hallucinogen USA? Most potent
Typical dose (20-80 ug) 1960’s ( ug) 5HT2A receptor agonist

Hallucinogens: Dissociative Anesthetics
Phencyclidine - Angel dust, PCP Ketamine - Special K NMDA Glutamate receptor antagonists Nystagmus

Opioids Opiate: natural alkaloid derivatives opium poppy
- Morphine (MS Contin), Codeine - Heroin (diacetyl morphine) - Urine toxicology screen detected Semi-synthetics - Hydrocodone (Vicodin) - Oxycodone (Oxycontin or Percocet) - Oxymorphone (Opana) - Urine toxicology screen detection erratic Synthetics - Methadone - Fentanyl (Duragesic; Actiq) - Buprenorphine (Subutex) - Urine toxicology screen undetected

Endogenous Opioid System
Receptors - Mu: euphoria, analgesia, ↓ breathing/muscle tone - Delta: ↓ breathing, euphoria - Kappa: analgesia, sedation, miosis Endorphins - β-endorphine: mu and delta - Enkephalins: delta - Dynorphins: kappa

Opioid Full Agonists activates the mu receptor is highly reinforcing
Full agonist binding … activates the mu receptor is highly reinforcing is the most abused opioid type includes heroin, codeine, & others

Opioid Partial Agonists
Mu receptor Partial agonist binding … activates the receptor at lower levels is relatively less reinforcing is a less abused opioid type includes buprenorphine

Opioid Antagonists occupies without activating is not reinforcing
Antagonist binding … Mu receptor occupies without activating is not reinforcing blocks abused agonist opioid types includes naloxone and naltrexone

Comparison of Activity Levels
Partial Agonist

Mechanisms of Action Block DA/5HT/NE transporters Cocaine Amphetamines
MDMA Cathinones Modulate receptors Opioids Cannabinoids Nicotine LSD Psilocybin Mescaline Modulate ion channels Alcohol PCP Ketamine Most that block/release from dopamine transporter also act at serotonin and often norepinephrine transporters as well: Amphetamine DA > 5HT, MDMA 5HT > DA Often multiple mechanisms some (many?) of which we are unaware.

Alcohol: Naltrexone Mu opioid receptor antagonist
↓ Positive reinforcement (reward, craving) ↑ Time to first drink and to heavy drinking ↓ Percent drinking and heavy drinking days Oral 50 mg daily → adherence an issue Intramuscular 380 mg monthly Contraindicated Acute hepatitis Liver failure Need for opioids

Alcohol: Naltrexone Functional polymorphism in mu opioid receptor
Asn40Asp increases beta endorphin binding 3 fold, present in 24-36% of Europeans Individuals with Asp40 variant with greater response to naltrexone

Alcohol: Acamprosate Inhibits/modulates glutamate receptors
↓ Craving/dysphoria and anxiety ↑ Time to first drink and to heavy drinking ↓ Percent drinking and heavy drinking days Oral 666 mg three times daily Contraindicated in severe renal disease

Alcohol: Disulfiram Alcohol → Acetaldehyde → Acetate
Irreversibly inhibits acetaldehyde dehydrogenase Acetaldehyde accumulates Flushing Nausea Vomiting Most studies negative, supervised maybe helpful mg daily Monitor liver function, caution with heart disease

Opioids: Naltrexone Mu opioid receptor antagonist
Oral 50 mg daily → adherence an issue Intramuscular 380 mg monthly May be effective select populations Contraindicated Acute hepatitis Liver failure Need for opioids

Opioids: Buprenorphine
Mu opioid receptor partial agonist Combined with naloxone ↓ diversion ↑ Retention in treatment ↓ Heroin use Average 8-16 mg daily, max 24 mg daily Buprenorphine waiver (DEAX) to rx

Opioids: Buprenorphine
Mu opioid receptor availability Greenwald et al, 2003

Opioids: Methadone Mu opioid receptor agonist
↓ Heroin use/HIV 4x/criminal activity 50% ↑ Employment 25% 1st day ≤ 40 mg, target range mg 40 mg blocks withdrawal, higher for craving For SUD treatment only in methadone clinics For withdrawal can use on inpatient medicine Criteria for use - ≥ 18 yo - Most meet criteria for dependence for 1 yr Side effects Minimal sedation once tolerance achieved Constipation, talk to pts about bowel program Increased appetite/weight gain Lowered libido, may decrease gonadal hormone levels Limited evidence other long-term side effects

Misuse: Definition Use without a prescription (rx)
Use of rx in manner other than rx More often Larger dose Longer period Purpose/reasons Self-treating medical condition Other: euphoria, coping, concentration Nonmedical use/Misuse/Inappropriate use

New Misusers in Past Year
SAMHSA, NSDUH 2006 and 2007

Source of Opioid Pain Relievers

Problems with Rx Opioids
Nonmedical use - Tripled - 12 million Problems with use - ↑ 27% - 1.9 million Emergency room visits - Doubled - 475,000 Xanax – alprazolam, Ativan – lorazepam, Valium – diazepam, Klonopin – clonazepam Morphine (MS Contin), Codeine, Vicodin – Hydrocodone, Oxycontin/Percocet – Oxycodone, Opana – Oxymorphone Treatment admissions - Doubled - 754,000

Primary non-heroin opioid admission rates (per 100,000)
Admissions: 1999 Primary non-heroin opioid admission rates (per 100,000) Per 100, 000 73

Admissions: 2001 Primary non-heroin opioid admission rates (per 100,000) 74

Problems with Rx Opioids
Nonmedical use - Tripled - 12 million Problems with use - ↑ 27% - 1.9 million Emergency room visits - Doubled - 475,000 Treatment admissions - Doubled - 754,000 Xanax – alprazolam, Ativan – lorazepam, Valium – diazepam, Klonopin – clonazepam Morphine (MS Contin), Codeine, Vicodin – Hydrocodone, Oxycontin/Percocet – Oxycodone, Opana – Oxymorphone Overdose Deaths - Tripled - 16,651

Prescribing Precautions
Careful diagnosis and psychosocial assessment Align physician and patient expectations Structured care - Decrease symptoms - Improve function - Minimize adverse effects of medications - Minimize risk for misuse or SUD Reassess, monitor, and document

Acute pain – opioids highly effective
Opioids: Pain Acute pain – opioids highly effective Cancer pain – opioids highly effective Chronic non cancer pain % U.S. adults with chronic pain - Impacts employment - Impacts health - Evidence opioids effective very limited

Opioids: WHO Analgesic Ladder

Opioids: Analgesic Ladder Expands

Opioids: Analgesic Platform

Opioids: Use Alternatives
Physical therapy, biofeedback Cognitive behavioral therapy, psychotherapy Mind-body integration (yoga, meditation) Hypnosis, relaxation therapy NSAIDS (ibuprofen, naproxen, celecoxib) Muscle relaxants (baclofen, dantrolene) Anticonvulsants (gabapentin, pregablin) Antidepressants (TCAs, SSRIs, SNRIs) Surgical and neurosurgical interventions

Benzodiazepines: Anxiety
Level of evidence for BZDs Meta-analysis/replicated RCT → ↓ symptoms Panic disorder/Generalized anxiety disorder Short term efficacy studies, 4-8 weeks Recommended short term use, 1-3 months RCT/small trail → ↑ symptoms Obsessive compulsive disorder Post traumatic stress disorder No evidence of benefit beyond therapy Simple phobia

Benzodiazepines: Insomnia
Level of evidence for BZDs/Z-Drugs Meta-analysis/replicated RCT → ↓ symptoms Short term efficacy studies Recommended 2-4 weeks 2 RCTs Other conditions treated with BZDs Hypnotic – anaesthesia, surgery premedication Anticonvulsant – status epilepticus Muscle relaxant – spasm, spasticity, paraplegia Involuntary movements – myoclonus, restless legs Alcohol withdrawal Z-Drugs Effective daily or intermittent use – 6 months

Benzodiazepines: Use Alternatives
Therapy, Therapy, Therapy Insomnia → 1st tx = sleep hygiene Anxiety → 1st med = SSRIs, venlafaxine Insomnia → 1st med = Z-Drugs? > BZDs Insomnia → Doxepine 3-6 mg Insomnia → Ramelteon – melatonin R agonist Gabapentin/pregablin – comorbid chronic pain Antihistamines/Trazadone Sedating antipsychotics

Benzodiazepines: Dose Zones
Green light zone: ≤ ½ max dose PDR Anxiety patients without SUD Yellow light zone: ½ - max dose PDR Not many anxiety alone patients Red light zone: > max dose PDR SUD patients reach quickly

Benzodiazepines: Doze Zones
Lorezepam ≤ 5 mg/d 5 -10 mg/d > 10 mg/d Clonazepam ≤ 2 mg/d 2 - 4 mg/d > 4 mg/d Diazepam ≤ 20 mg/d 20-40 mg/d > 40 mg/d Alprazolam Alprazolam XR ≤ 3 mg/d 3 - 6 mg/d > 6 mg/d

The End

Substance Use Disorders

Similar presentations

Presentation on theme: "Substance Use Disorders"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Substance Use Disorders

Similar presentations

Presentation on theme: "Substance Use Disorders"— Presentation transcript:

Similar presentations

About project

Feedback