Marijuana Use in Pregnancy and Post Partum (Pinto 6/7/2022)

Many thanks for an excellent Grand Rounds year-- we covered a wide range of topics from Drowning Prevention to Moral Distress, from CKD to Gender Expansive Care, from Racism in Medicine to Bias in Documentation, from Breast Cancer Reconstruction to Alcohol Withdrawal. And more!

Also thanks to our last Grand Rounds speaker of the year, Dr. Vanessa Pinto, who gave an excellent talk on Marijuana (MJ) in pregnancy and postpartum. 

A recording of her presentation is available HERE. 

My notes: 

• In 15-44 year old pregnant patients, 4.9% reported MJ use in the last month during pregnancy (compared to 11% when not pregnant)
• Use during pregnancy has increased since 2015, with significant increases during pandemic
• 44.6% of patients who reported smoking MJ before the pregnancy continued use during pregnancy
• Risks of MJ use during pregnancy include low birth weight, preterm birth (when combined with tobacco), still birth, and long term neurodevelopmental issues
• There are some women that believe that MJ is helpful for hyperemesis and nausea/vomiting of pregnancy. However, there is no data to support this. And we know MJ use is associated with cyclic vomiting syndrome. 
• The only state with legislation to caution use of MJ in pregnancy in Oregon

MJ in Pregnancy

MJ crosses the placenta; it also influences the physiology of the placenta. THC crosses most readily. Can enhance permeability to other substances, has an influence on uterine blood flow, increases placental resistance, reduces circulation, and impairs gas exchange. 

There are two large systematic reviews looking at effect of MJ on the neonate. Unfortunately, the few studies we have did not exclude patients with polysubstance use. It is believed that MJ use is associated with anemia, low birthweight, and increased rate of NICU transfers

Newborns exposed to MJ display altered arousal, increased excitability, tremors, exaggerated startle reflex, abnormal sleeping patterns. However, there is no data to support MJ withdrawal syndrome (like we see in opiates). Endocannabinoid receptors are seen as early as 5 weeks gestation.

MJ in Breastfeeding

MJ gets readily into breastmilk. It is a small lipid-soluble molecule and readily passes. There are not large studies looking at effect on infants, but many mothers using MJ are also using alcohol, other illicit substances and/or tobacco. 

ACOG (2017): "Insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding and in the absence of such data, marijuana use is discouraged."

AAP (2012):  "Street drugs such as PCP, cocaine, and cannabis can be detected in human milk, and their use is. . . of concern, particularly regarding the infant's long-term neurobehavioral development, and thus are contraindicated."

The Academy of Breastfeeding Medicine: "A recommendation of abstaining from any marijuana use is merited. At this time, although the data are not strong enough to recommend not breastfeeding with marijuana use, we urge caution."

Counseling and education

Substance use counseling changes behavior. Clinicians/providers should be counseling women who use MJ during pregnancy and postpartum period of the risks and advise them to stop. 

1) Advise patients that MJ should not be used during pregnancy.

2) IF patients screen positive for MJ, counsel and refer to treatment, if indicated.

3) Emphasize purpose of screening is to allow treatment, not punishment.

4) Pregnant patients with MJ use can be subject to CPS investigations.

5)Discourage MJ use while breastfeeding.

Management of GHB/GBL Drug Overdose and Withdrawal Syndrome (Steinberg 3/2022)

Thanks so much to Dr. Gabrielle Steinberg for her excellent presentation on Atypical Addictions: GHB/GBL Drug Overdose and Withdrawal

A recording of Dr. Steinberg's excellent presentation is available HERE. 

We know that addiction is a huge problem worldwide

• Globally, 33.6 million people suffer from substance use disorder (2019)
• In the US between 1999-2020, 841,000 people died  from drug-related overdose
• Synthetic opioids are main driver for SUD related deaths (esp. fentanyl right now)
• In 2011, Drug Abuse Warning Network (DAWN 2011) reported 2.5 million drug use/misuse related ER visits, more than half from multiple drugs: alcohol, cocaine, marijuana, opioids, methamphetamines
• Atypical/uncommon drugs comprise about 5% of ER visits
• GHB/GBL was associated with 2, 406 ER visits in 2011 (US)
• Other "atypical substances": inhalants/solvents, bath salts, Khat, K2/spice, Kratom, U47770, Rohypnol, DMT, MPTP

GHB=gamma hydroxybutyrate

GBL= gamma butyrolactone 

GBL is a precursor to >> GHB is a precursor to>> GABA

GHB is a CNS depressant, also has effect on mesolimbic pathway (rapid reward, abuse potential)

Initially developed in  France as general anesthetic (not in US), can be prescribed in salt form (prescription rx approved to tx narcolepsy, cataplexy). In 1980s, marketed as supplement for body builders, removed from the market due to fatal intoxications/overdose

GHB= schedule 1 (no current recognized medical use, high potential for abuse)

When used illicitly, GHB is used for calming, euphoric effects, aphrodisiac (increases libido).

Considered similar to MDMA/alcohol. 

Also "date rape drug" because of effects on memory and consciousness

• colorless odorless liquid, or white powder that can be dissolved
• mostly ingested orally as liquid, sometimes pill form
• onset: high 15-30 minutes, duration 3-6 hours, doses vary
• tolerance and dependence does build quickly
• death has been associated with overdose, withdrawal and intoxication 

Demographic & use patterns: majority male, majority white, late 20s/30s (same in ED overdose data, though increasing rates GHB overdoses in women), commonly co-ingested with alcohol

GBL now becoming more common than GHB, cheaper, easier to access: found in solvents, greater potency, faster onset

GHB/GBL intoxication

CNS depression, agitation, seizures

Hypothermia, bradypnea, bradycardia (hypotension less common), urinary and fecal incontinence

death from intoxication/overdose can be caused respiratory depression and/or respiratory arrest, aspiration (due to risk for vomiting)

Common to see alternating ABRUPT onset somnolence and agitation

Toxicity can come on and resolve abruptly, effects last 2-5 hours

Hospital stays can be often short because of short half life (managed out of ER and then discharged)

Most of the time GHB/GBL used with other drugs (ETOH, methamphetamines)

Not detected on typical urine drug screen, do have a send out confirmation test (urine test takes 9-10 days to result)

Key to management GHB intoxication: supportive care, airway support (intubation to protect airway when sedated), use of sedation due to abrupt alertness that can occur (midazolam, propofol), best effects with benzos (lorazepam or diazepam) or Haldol

There is no antidote, no effect from naloxone or flumazenil

GHB/GBL withdrawal

Happens quickly, as early as 6 hours after last dose

Mild/mod: anxiety, tremor, diaphoresis, tachycardia

Severe: agitated delirium, seizures, hypothermia, rhabdomyolysis

Preferred treatment: benzodiazepine (PO valium for longer duration), baclofen TID has been studied (shown to reduce withdrawal, reduce cravings, GABA b receptor agonist, small studies)

For severe withdrawal: intubation, IV valium benzo of choice. Can get benzo resistance (acts more on GABA-A receptors). Add on Propofol, Precedex.

Vitamins: magnesium, folate (some Wernicke's like syndrome)

Fluid resuscitation: vomiting, diaphoresis

No validated withdrawal scale, most literature uses CIWA scores

Netherlands study (450 patients): giving GHB taper in the hospital, taper down and off, relatively effective

Belgium tried similar protocol with benzos (less effective)

Outpatient management of GHB/GBL

GHB/GBL use is associated with high risk of abuse, rapid onset of euphoric and calming effects

outpatient labs: GHB urine drug screen is available via Quest labs/ECW (send out, takes some time)

GHB/GBL addiction hard to treat outpatient

Study from Netherlands (596 pts): high rates of relapse with GHB use, withdrawal severity, ER visits, duration of time in treatment programs

Baclofen has been found to be helpful w/detox, but also in maintaining abstinence, no RCTs; one non-RCT found baclofen 45-60mg/day  (10-20mg TID, titrate by patient) PLUS CBT more effective in reducing craving, anxiety, and relapse (than CBT alone). Baclofen decreases need for benzos

Key to outpatient management is wrap around support with interdisciplinary team: more success with patients with lower daily dose. 

Outpatient Rx should include: baclofen PLUS valium/diazepam (symptom guided) PLUS close follow-up PLUS simultaneous behavioral therapy

For help/assistance with these atypical drugs, consider reaching out to the UCSF Substance Use Disorder Warmline https://nccc.ucsf.edu/clinical-resources/substance-use-resources/

855-300-3595.

Primary Care of Alcohol Use Disorder (Lund 5/20/2020)

Thanks to Dr. Erin Lund, who gave an excellent Grand Rounds presentation this week on the Primary Care of Patients with Alcohol Use Disorder. Dr. Lund encouraged primary care providers to be forward thinking and proactive about diagnosing and treating alcohol use disorder.

Here's the quick and dirty: 1) AUD is super common 2) Screen for AUD 3) Start with brief interventions, and 4) Offer medications when indicated. Keep reading, you'll feel much more comfortable once you have a few of Dr. Lund's tools in your toolbox.

Alcohol use disorder (AUD) is SUPER common in the US with a 12-month overall prevalence of almost 14% of adults (7% mild, 3% moderate and 3.4% severe).

• Lifetime prevalence of AUD is is 29% (13% lifetime prevalence of severe AUD)
• Men>>women, Young>old
• Alcohol is the 3rd leading cause of death from modifiable risk factors (behind smoking and obesity/poor diet)
• Genetics definitely play a role: 5-10% of women and 25% of men have a relative with AUD

A little reminder about what is considered "one drink" when you ask a patient how much they drink:

Remember, however  that different beers and wines have different alcohol contents, so it's not uncommon that people are drinking 'more' than they realize.

How much is too much?

• Binge Drinking: at least 1 day in the past 30 days with >4 drinks for a woman, >5 for man on one occasion
• Heavy Alcohol Use: binge drinking more than 5 days (in the past 30 days)
• Drinking limits (cut offs for low risk vs. high risk drinking) are based on both gender AND age. 

**Note: for people over 65, limits are the same for men and women: no more than 3 drinks/day or 7 drinks/week.

**Note also that many people you know and love meet criteria for at least a mild AUD; this may be particularly true in this land of wine country and craft beers.

DSM-5 criteria for Alcohol Use Disorder : a maladaptive pattern of substance use with 2 or more of the following 11 criteria within past 12 months (Mild 2-3 criteria, moderate 4-5, severe ≥ 6)

1. Drinking larger amounts/longer periods than intended
2. Effort/desire to cut down
3. Great deal of time spent obtaining, using, and recovering
4. Craving
5. Recurrent failure to fulfill role
6. Continued use despite social/interpersonal problems related to drinking.
7. Activities given up (social, occupational, recreational)
8. Recurrent physically hazardous behavior.
9. Continued use despite physical or psychological problems
10. Tolerance
11. Withdrawal

Why screen for risky drinking?

• It's a USPSTF Grade B recommendation 
• AUD is really common; harmful drinking is estimated at 30% in primary care practices 
• Patients with AUD have a higher risk of death by ALL causes
• Plus, they die years earlier, increased automobile crashes, accidental and intentional injury, social and legal problems
• AUD affects every organ and system in the body: from brain (sleep, mentation) to gut (gastritis, cancers) to heart (cardiomyopathy, CAD)

How to screen? Two options;
1) Single question alcohol screening test (NIAAA): How many times in the past year have you had more than  X or more drinks/day? (X=4 for a woman and X=5 for a man) (>1 is a positive screen, 82% sens, 79% specificity)
2) AUDIT-C

Addiction medicine specialists use a format called SBIRT when talking about how to intervene. (SBIRT stands for Screening, Brief Intervention, Referral to Treatment)Brief Intervention:

You can use the AUDIT C to screen, but also to guide treatment ad your intervention:

0-3: health promotion (great job, keep it up! you are drinking responsible)

4-5: moderate risk drinking, brief intervention

6-7: high risk drinking, brief intervention +/- meds +/- specialty care mgt

8-9: severe risk drinking: start meds, psychosocial intervention, specialty mgt

10-12: specialty management

Here is an example of a brief intervention called FRAMES: 

Treatment for AUD includes 1) acute treatment of AUD (intoxication and withdrawal) AND 2) chronic treatment (abstinence initiation, use reduction, and relapse prevention)

• Psychosocial: formal therapy, self/help 12-step (There are LOTS, including AA, SMART Recovery, Rescue Recovery, and more). Each have varying levels evidence and should be tailored to patient's preferences
• Local resources available HERE, click to explore what is available in Sonoma County
• Medications???

Okay, what about the meds, do they actually work? 

• Pharmacologic management of AUD is underutilized in primary care
• AUD is one of only 3 substances with THREE FDA-approved medications
• Disulfiram (aka Antabuse)
• Acamprosate
• Naltrexone (oral vs. extended release injectable)
• Only 8% of adults with AUD in the US are treated with medications!
• There are also LOTS of medications with varying degrees of evidence used (off label) for AUD, including topiramate, baclofen, gabapentin, ondansetron and sertraline (more below)

Acute Alcohol Withdrawal (AWS):

• Look for signs of sympathetic nervous system hyperactivity: HR, BP, pupils, diaphoresis, tremor
• Use the CIWA vs. Short Alcohol Withdrawal Scale (SAWS) to characterize severity of the AWS: patient scores symptoms, <12 mild AWS, >12 moderate to severe AWS
• CIWA takes 2 minutes, assess 10 (mostly subjective) symptoms
• SAWS is completed by patient, validated in the outpatient setting



SAWS, AAFP 2013

Inpatient vs. outpatient management of AWS?

• 90% of patients with AWS can be managed outpatient
• Must be able to take oral meds, return for frequent follow-up visits, have a friend/relative/caregiver to watch for red flags
• Contraindications to outpatient management: serious lab abnormalities (e.g. profound anemia), hx of withdrawal seizures or DTs, serious medical or psychiatric comorbidity, current polysubstance use
• FYI: Supervised detox (with meds rx'd by YOU for symptom management) is available at Orenda Center. Call: 707-565-7460
• There is evolving evidence for the use of both anticonvulsants (e.g. valproic acid, carbamazepine, and more, see table) and gabapentin to treat AWS

Oral medications to treat AWS (AAFP 2013)

 A little more on the FDA approved meds to treat AUD. While none have great evidence at abstinence, they all have varying evidence for reducing quantity, frequency, etc. They are worth offering in shared decision-making conversations:

• Disulfiram (Antabuse): not really recommended by Dr. Lund because it doesn't really work
• oldest med around for AUD (approved in 1949)
• makes you sick when you drink, inhibition can last for days (up to 14)
• Two blinded studies in 2014 showed no better than placebo in reducing overall ETOH consumption
• Acamprosate,  2 tabs TID (1998 mg/day), covered by PHP
• short half life: has to be dosed so frequently
• NNT 12 to return to "any drinking", can use in people who are still drinking
• may be more effective in women, particularly women with anxiety
• Naltrexone (oral vs. injectable), covered by PHP
• oral tabs 50mg daily, injectable 380 mg IM/month
• oral NNT 20 to prevent return to 'any drinking', NNT 12 to prevent return to 'heavy drinking'
• injectable: reduces number of drinking days
• cannot be combined with opiates, cannot use in cirrhosis

Other meds (non FDA approved) with emerging data for AUD

• Topiramate: A 2014 meta-analysis found it more effective than naltrexone and acamprosate, particularly for increasing abstinence and reducing heavy drinking. Dosing: start with 25mg/day titrate up slowly by 25-50mg per week. Goal: 100-300 mg/day, divided BID
• Gabapentin: 2014 RCT found reduced craving and increased abstinence. Effective dose for relapse prevention: 600 mg TID, small abuse potential (esp in opiate use disorder), can be combined with naltrexone to increase efficacy. Can be sedating.

Okay, don't you feel braver!? Go out and heal, and remember: screen, intervene, and offer meds (when appropriate).

Methamphetamine Use Disorder (Nicholson, 1/8/2020)

Thank you so much to Dr. Lisa Nicholson for her excellent presentation this week during Grand Rounds on Methamphetamine Use Disorder.

Most of you are well aware that methamphetamine has some health effects and societal implications, but did you know that our very own health care system and pharmaceutical companies are responsible for introducing methamphetamine to our military pilots in WW2 (to keep them awake), to the general market OTC in 1939 (brand nameBenzedrine) and is still available even today with a prescription?

Meth has been marketed for the treatment of depression, obesity, fatigue, low libido, inattentiveness, menopause, nasal congestion, asthma, and even the common cold. (Check out the ads to the Right) 

Methamphetamine is typically smoked, inhaled, or ingested. In California, the majority of people who use meth smoke it, but in Texas, the majority inject it.

·        1.2% of Californians have used meth in the last year

·        6% of Sonoma County 11^th graders have tried meth (yikes!)

·        Meth is the most common illicit substance used worldwide (after MJ)

·        In Sonoma County, meth is by far the most commonly used substance in families involved with the Sonoma County court system implicated in the abuse or neglect of children (second to alcohol)

This is MIND-BLOWING! Meth is the most addictive substance that exists: 47% of people will become addicted after first use, 60% after second use

Medical implications of meth use:

·        Acute intoxication: malignant hypertension, stroke, cardiac arrest, meth psychosis

·        Post-meth: altered mental status, irritability, violence

·        Long term: meth cardiomyopathy, dental problems, cerebral atrophy, mood disorders

A bit on Meth psychosis. . .

·        Up to 40% of users get meth psychosis, it is dose dependent, on average 1 week duration, but users with >5 years of use can have prolonged psychosis (>1 month).

o  If a patient has experience meth psychosis in the past, they are “sensitized” and more likely to experience it again in the future

·        Meth psychosis can mimic other mental illness: mania, schizophrenia, mood disorders.

o  At Zuckerberg SFGH inpatient psych facility estimates 47% of patients admitted to the inpatient ward are not mentally ill—they are high/coming down from meth (2019 study)

·        To distinguish primary psychosis from meth induced: you must have meth use BEFORE psychosis, and abstaining from meth likely will improve/make recede the psychosis

·        There is limited evidence on the use of atypical antipsychotics for thetx of meth psychosis: generally olanzapine, quetiapine. There is also evidence for the use of benzodiazepines for the treatment of meth withdrawal

A bit on hypertension. . .

Severe hypertension of meth should be treated with BETA BLOCKERS: labetolol. Tachycardia can be treated with  metoprolol (correct the catecholamine flood)

Patients with severe hypertension and chest pain are at risk for acute MI, dissection, and/or aortic aneurysm. Get a head CT if you cannot examine them thoroughly.

Meth cardiomyopathy very common (usually dilated non-ischemic, VERY low EF ~10%).

A 2017 German study found that with meth abstinence average EF increased from 20% to 43%, so STOPPING METH can improve cardiac function markedly!!!

There are no FDA approved treatments for meth use disorder. Mixed evidence for:

·        Bupropion (Wellbutrin): blocks dopamine reuptake, can help in early abstinence, modest evidence, not recommended after 4 weeks abstinence (can be triggering)

·        Mirtazapine: helps with sleep, appetite, modest reduction in meth use

·        Naltrexone: appears to decrease meth high and cravings, mixed results

·        Modafinil (Provigil): some evidence in cocaine use disorder, 2010 RCT said no better than placebo for meth

·        Adderall/Ritalin: jury still out

      

Psychosocial approaches:

Best evidence in non-pharm management of patient is for contingency management (=monetary or other tangible short term rewards for abstinence)PLUS Community reinforcement (healthy restructuring of social environment)

Not great evidence for 12-step, CPT or supportive therapy. Hmmm. No one in Sonoma County appears to currently be using contingency management—MediCal does Not cover it

Don’t forget harm reduction in patients with meth use disorder:

1)     Condoms 2) PrEP 3) Needle exchange (when appropriate) 4) Dental Care 5) Clinic structures that don’t punish people for no-shows, tending more to drop-in