CO-OCCURRING DISORDERSIn Substance Abuse

Part III: Treatment of COD,with focus on psychotropic medications

A Workshop for Alameda CountySUD Treatment Providers

March 25, 2016Rob Lee, MD

Some Addiction Statistics

• 18% of Americans will develop SUD (Substance Use Disorder) over their lifetimes

• 40-50% of Americans with Severe Mental Illness will develop SUD. Those with SMI are half of all addicts = CoOccurring Disorders

• Best Addiction Treatment yields a sustained recovery rate of 50%

• For those with CODs, Best Treatment typically yields only 25-30% sustained recovery

Treatment of Co-Occurring Disorders

• Abstinence and social support of abstinence (eg, 12-Step)

• Education around SUD and Mental Health Disorder

• Social amelioration, including housing (Case Management)

• Treatment of medical conditions

• Psychotherapy when possible

• Psychotropic Medications when useful

• Neuromodulation in some cases: The future of treatment?

Psycho-Active Substancesvs Psycho-Tropic Medications

• PsychoActive substances are a huge group of foods, herbs, chemicals, and medications that alter the way the brain functions. Historically, many of these are addictive.

• PsychoTropic meds are a subgroup of PsychoActives that alter the brain in ways that are considered beneficial. The great majority of these are non-addictive.

Psycho-active drugs

alter the function of the

cognitive-emotional

mechanism of the

brain, called The Limbic System.

Psycho-tropic drugs

generally decrease the

activity of one or more

Limbic System

component, typically

the Amygdala or

Nucleus Accumbens

(here designated

“Basal Nuclei”)

History Of Psychoactive Substances• Since ancient times humans have shown attraction to

substances that alter brain function: And until the past 100 years most of them have been addictive!

• Alcohol use is extremely ancient and pan-cultural

• Indo-Levant: Opium, Marijuana, Tea, Betel

• Africa: Coffee, Khat, Ibogaine

• New World: Tobacco, Coca, Peyote, Psilocibin

• The first synthetic psychoactives were made in the late 1800s: Barbiturates (Germany), Amphetamines (Japan)

History of Psychotropics• Oddly, these are almost all synthetic, not derived from

plants or other natural sources

• Lithium was discovered in 1947, tho not used until the 1960s

• 1950s: Thorazine-type antipsychotics (1G-APs), MAOI antidepressants, Tricyclic antidepressants

• 1960s: Valium-type anxiolytics (benzodiazepines)

• 1980s: Prozac-type antidepressants (SsRI) and Wellbutrin (NsRI)

• 1990s: Clozaril & Zyprexa and other 2G-antipsychotics; Effexor and other SNRI antidepressants

The Pharmaceutical Industry and Psychotropics

• There are around 200 pharmaceuticals manufactured and sold for their psychiatric psychotropic effects

• This is about 10% of all the meds in the US Formulary

• About 3 new psychiatric psychotropics are introduced each year

• Medication development takes ~20 years and is extremely expensive (~$1-5 billion per successful drug)

• Nonetheless, psychotropics are a lucrative market, because they are often used for years

The Major Co-Occurring Disorders and Psychotropic Medications

• Bipolar Disorders: Medications are necessary

• Psychosis Disorders: Meds almost always needed

• Depression Disorders: Meds necessary in some cases, helpful in most

• Anxiety Disorders: Meds necessary in some cases, helpful in many

• ADD: Meds helpful in moderate and severe cases

• Post-Traumatic Disorders: Meds are not generally indicated but are helpful temporarily in many cases

• Eating Disorders: Meds not generally indicated, but sometimes helpful

• Personality Disorders: Meds not generally indicated, occasionally helpful

Classes of Psychotropic MedicationUsed in Psychiatry

• Mood Stabilizers: Lithium and Valproate (Depakote), etc

• AntiPsychotics: Olanzapine (Zyprexa), etc

• AntiDepressants: Fluoxetine (Prozac), etc

• Anxiolytics: Valium and Buspar, etc

• PsychoStimulants (ADD meds): Ritalin, etc

• Sleep Meds (Hypnotics): Trazodone and Ambien, etc

• AntiAddiction Meds: Methadone and Naltrexone, etc

Medical Psychotropics

• Pain Medications

• Epilepsy Medications

• Anesthetics

• Anti-Dementia Medications

• Anti-Parkinsons Medications

• Anti-Narcolepsy Medications

• Weight-loss Medications

• Etc

AntiAddiction MedicationsMedication-Assisted Treatment (MAT) traditionally refers to the

use of methadone or buprenorphine to treat opioid addition

Methadone for addiction is available only through closely regulated clinics. Significant stigma.– Effective for addictions of any severity and has high

client retention. But has high mortality risk (the most dangerous opioid) and high street value

Buprenorphine (Suboxone) is available through private medical offices. Less stigma.– Effective only for mild-moderate addiction, and

less client retention. But low mortality risk and less street value.

Harm Reduction Treatment

• Primary aim of treatment is to reduce the social-mental-physical harms of addiction: Isolation, poverty, crime, illness, early death.

• Abstinence is a secondary goal, and treatment is continued even if Substance Use is not completely stopped.

• More effective for some (50%?) but not for all with SUD. May be less effective for those with more severe CODs.

AntiAddiction Medication:Medication Assisted Treatment of Alcoholism

• Naltrexone (ReVia and Vivitrol)

• Acamprosate (Campral)

• Disulfiram (Antabuse)

• [Topiramate (Topomax)]

• [Gabapentin (Neurontin) or Pregabalin(Lyrica)]

Anti-Addiction Medication:

MAT of Nicotine Addiction

• Nicotine patches +/- gum or spray

• Bupropion (Zyban or Wellbutrin)

• Varenicline (Chantix)

AntiPsychotic Medications• Second-Generation AntiPsychotics (“2GAPs”, introduced since ~1990) are

dominant. There are eleven now, but these are the most important:

– Olanzapine (Zyprexa)

– Risperidone (Risperdal): Also available as a monthly injection.

– Quetiapine (Seroquel)

– Aripiprazole (Abilify) [$$$]: Also available as a monthly injection.

– Clozapine (Clozaril)—the most effective but requires frequent blood tests

• A few First-Generation AntiPsychotics (“1GAPs”, introduced before 1980) are still used: Haloperidol (Haldol) and perphenazine (Trilafon) seem most common. These meds are clearly more toxic to the brain than the 2GAPs, and their use should be avoided except in special circumstances.

Mood Stabilizer Medicationsto treat Bipolar Disorder

• 2GAPs are effective and approved to treat BD and are probably the dominant BD meds at this time

• Lithium

• Valproate (Depakote)

• Lamotrigine (Lamictal)

• Carbamazepine (Tegretol) and oxcarbazepine (Trileptal)

• Lurasidone (Latuda) [$$$$]—a newer expensive(2010) 2GAP

AntiDepressants:Serotonin-selective Re-uptake Inhibitors (SsRIs)

• Fluoxetine (Prozac)

• Sertraline (Zoloft)

• Citalopram (Celexa)

• Escitalopram (Lexapro)

• Paroxetine (Paxil)

• Fluvoxamine (Luvox)

AntiDepressant Medications:Serotonin+Norepinephrine Re-uptake Inhibitors (SNRIs)

• Venlafaxine (Effexor)

• Duloxetine (Cymbalta) [$$]

• Milnacipran (Savella) [$$$]—newer (2009),used mainly for pain

• Desvenlafaxine (Pristiq) [$$$]—newer (2008)

• Levomilnacipran (Fetzima) [$$$]—new (2013)

AntiDepressant Medications:Others

• Bupropion (Wellbutrin)--the only NsRI for depression

• Mirtazapine (Remeron)

• Nortriptyline (Pamelor)--tricyclic

• Amitriptyline (Elavil)--tricyclic, used mainly for sleep & treatment of chronic pain

• Vilazodone (Viibryd)--new (2011) [$$]

• Phenelzine (Nardil)--an MAO-Inhibitor, rarely used now

Anxiolytics: Benzodiazepines(There are 14 sold in the USA)

• Diazepam (Valium)—long half-life

• Clorazepam (Klonopin)—long half-life

• Chlordiazepoxide (Librium)—long half-life, probably the lowest addiction risk

• Lorazepam (Ativan)—moderate half-life

• Temazepam (Restoril)—a very addictive med

• Alprazolam (Xanax)—a very addictive med

Anxiolytics:Non-Benzodiazepines

• SsRI AntiDepressants are generally effective for anxiety if used at lower doses and carefully titrated. These are now the dominant meds used for anxiety.

• Buspirone (Buspar)

• Hydroxyzine (Vistaril, Atarax)—An antihistamine

• Pregabalin (Lyrica) [$$$] and Gabapentin (Neurontin)

Psychostimulants:

Medications for ADHD

• Methylphenidate (Ritalin): short-acting, but there are formulations designed for longer half-life [$$]

• Amphetamine + dextroamphetamine (Adderall): short-acting, but there are formulations designed for longer half-life [$$]

• Bupropion (Wellbutrin)

• Gaunfacine and Clonidine

• Atomoxetine (Strattera) [$$$]

• Lisdexamfetamine (Vyvanse), new (2012) [$$$]

Hypnotics:

Medications for Temporary Insomnialasting 2 weeks or less

• Benzodiazepines: clonazepam (Klonopin), lorazepam (Ativan), diazepam (Valium)

• Zolpedim (Ambien) or eszopliclone (Lunesta) or zaleplon (Sonata)

• Not Recommended: triazolam (Halcion), temazepam (Restoril), flurazepam (Dalmane), opioids, older sedatives such as barbiturates

Hypnotics:Non-GABA-inducing sleep meds for persistent insomnia

• Trazodone

• Hydroxyzine (Vistaril, Atarax)

• Diphenhydramine (Benadryl, Nyquil)—OTC

• Low-dose tricyclics (amitriptyline (Elavil), doxepin (Sinequan))

• Melatonin—OTC (also available in expensive prescription forms)

• Low-dose mirtazapine (Remeron)

• Valerian root—OTC, an herb

• Suvorexant (Belsomra) [$$$]—new (2014) orexin receptor blocker

Neuromodulation TreatmentsNon-Invasive Methods

• Direct electrical stimulation of the limbic system can alter its function, often in positive and lasting ways

• ECT (Electro-Convulsive Therapy) has been in use since the 1930s. Uni-lateral and low-power techniques are now used and are safer.

• TMS (Transcranial Magnetic Stimulation) is now approved for MDD treatment: Neurostar device and several others. Requires a series of office appointments, typically 4-5x per week for 4 to 12 weeks. One course might cost around $12,000.

• CES (Cortical Electrical Stimulation) is approved since 1979 for anxiety/depression/pain, but it is still unclear if it really works. Device sold by prescription (~$500) for use at home by the patient.

Neuromodulation Treatments requiring minor surgery

• DBS (Deep Brain Stimulation): In use for many years for several severe conditions: Parkinsons, OCD, some epilepsy, possibly MDD. Electrodes are placed deeply into the limbic system, and the stimulator device is implanted like a pacemaker.

• VNS (Vagal Nerve Stimulation): An electrode is placed in the VN (in the neck) and used to transmit stimulation to the brain. The stimulator is implanted like a pacemaker.

• CBS (Cortical Brain Stimulation): Investigational only. Electrodes are placed surgically only to the surface of the frontal lobe(s). Otherwise similar to DBS.

Other “Treatments of the Future”

• Ketamine

• Better, longer-acting injection medications for chronic psychosis

• Imaging for early recognition and treatment (prevention?) of Mental Disorders

• Genetic therapies to treat/prevent brain-based Mental Disorders

• Ibogaine for addiction? [Risk of cardiac arrest]

Acupuncture

• There is substantial evidence that acupuncture can benefit mood and anxiety disorders

• Not recommended as primary treatment for BD or psychosis

• Generally requires multiple treatments/visits, sometimes for prolonged periods

• Is this a form of neuromodulation?

Limbic System Hygeine:Diet

• Hormones (corticosteroids, insulin, adrenalin, estrogens) have a major influence on limbic system function

• Diet and stress have a profound influence on these hormone systems

• As a rule: All CODs tend to worsen with a high-sugar, high-refined, high-stimulant diet

• High-fiber and high-antioxidant diets (vegetables and fruits) generally benefit CODs

• In certain cases, food additives, gluten, or specific “allergy” foods may be harmful

Limbic System Hygeine: Exercise

• Moderate consistent exercise is the Universal Remedy for all psychiatric conditions—and almost all medical conditions

• 30 minutes of fast walking (or equivalent) 5-6 days per week can be recommended in all cases

• More exercise is often better, but beyond 1 hour per day there is not much additional benefit for the psyche

• There are many Exercise Equivalents: Calisthenics, dancing, active yoga, gym workouts, etc, etc

Supplements

• Fish Oil (Omega 3 Fatty Acids) 3-9 grams per day

• Folic Acid (Folate) 800 mcg per day

• Vitamin D3 1000-2000 U per day, is probably advisable, tho there is controversy

• Multiple Vitamins possibly, if diet is not good

• Vitamin B12 for those with low-meat diet

• Vitamin E perhaps for those taking antipsychotics

Psychiatric Treatment in context of Long-Term Recovery

• There is a trend towards seeing medications as the best and most definitive treatment for CODs.

• In reality, medications rarely if ever cure CODs. The brain roots of mental disorder and addiction generally persist and the disorder may re-emerge despite continuing medication.

• The medication(s) may provide a better sail, but the hand on the tiller is most critical: This may be a counsellor and/or doctor for many years, but eventually the client’s own self-awareness should guide his lifelong discipline of recovery.

Our brains greatly make us who we are and who we become.

Yet also we are constantly making our brains, by each thing we do

and each thought we think.