How risky is cocaine use in pregnancy?

Early Hum Dev. 2012 Jun;88(6):333-7. Epub 2011 Oct 4.
Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach.
Mbah AK, Alio AP, Fombo DW, Bruder K, Dagne G, Salihu HM.
Department of Epidemiology and Biostatistics, University of South Florida, Tampa, FL
PMID: 21975278

The authors searched hospital discharge data to find 5000 women who used cocaine in pregnancy. These were matched to 5000 controls.  The patients were found by searching for ICD-9 diagnoses. 0.2% of these post partum discharges had a cocaine use diagnosis coded, 500 cases per year over 10 years.

They were compared for coded diagnoses indicating "placenta-associated syndromes": abruption, oligohydramnios, placental infarction, gestational hypertension, preeclampsia or eclampsia".

The authors used a propensity scoring algorithm"" to account for the effects of education, maternal age, race, tobacco use, parity, alcohol abuse, marital status, adequacy of prenatal care, gender of the infant, gestational diabetes, diabetes mellitus, year of birth and chronic hypertension

Increased for placental related pathology were found but not as high as some would have guessed.

Condition	Odds Ratio	Non Users	Users
Abruption	2.79	1.8%	5%
Oligohydramnios	1.23	2.0%	3.5%
Pre-eclampsia	1.33	3.3%	4.3%
Eclampsia	2.20	0.1%	0.2%

Some odds and ends about opiates

Case report of 3 patients showing cessation of intrathecal opiates causes withdrawal similar to other opiates and can be treated with similar protocols. These authors gave clonidine  for CIWA > 8 and IM buprenorphine for CIWA > 15.

Pain Pract. 2012 Aug 28.
Intentional Intrathecal Opioid Detoxification in 3 Patients: Characterization of the Intrathecal Opioid Withdrawal Syndrome.
Jackson TP, Lonergan DF, Todd RD, Martin PR.
Vanderbilt University Medical Center, Nashville, Tennessee
PMID: 22925591

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Not much LFT elevation with either methadone or buprenorphine

1269 patients randomized to either methadone or buprenorhine.  9 BUP and 15 MET participants showed extreme liver test elevations. These were attributed to hepatitis B and C during the study, or to active illicit drugs use during the first 8 weeks of treatment. They did note methadone patients were retained longer in treatment than buprenorphine patients.

Drug Alcohol Depend. 2012 Aug 22
Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: A randomized trial.
Saxon AJ, Ling W, Hillhouse M, Thomas C, Hasson A, Ang A, Doraimani G, Tasissa G, Lokhnygina Y, Leimberger J, Bruce RD, McCarthy J, Wiest K, McLaughlin P, Bilangi R, Cohen A, Woody G, Jacobs P.
Veteran's Affairs Puget Sound Health Care System, Seattle, WA 98108
PMID: 22921476

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A nice review of the treatment of opiate dependence in pregnancy

Psychosomatics. 2012 Aug 14. [Epub ahead of print]
Evaluation and Management of Opioid Dependence in Pregnancy.
Park EM, Meltzer-Brody S, Suzuki J.
Department of Psychiatry, University of North Carolina, Chapel Hill, NC.
PMID: 22902085

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Sci Transl Med. 2012 Aug 8;4(146):146ra110.
A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.
Wee S, Vendruscolo LF, Misra KK, Schlosburg JE, Koob GF.
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
PMID: 22875830

The authors find that giving buprenorphine together with full dose naltrexone blocks cocaine use, presumably due to kappa antagonism

Buprenorphine has potent μ opioid receptor partial agonist actions and κ opioid receptor antagonist actions. As a result, we hypothesized that the potent κ opioid receptor antagonist action of buprenorphine may decrease compulsive cocaine seeking. However, one major concern with the use of buprenorphine is that its μ agonist action during prolonged treatment may result in opioid dependence in previously non–opioid-dependent cocaine abusers. One way to minimize this effect would be to attenuate the μ action of buprenorphine by coadministering a μ receptor antagonist such as naltrexone. Naltrexone is a highly potent μ opioid antagonist with weaker δ and κ antagonist properties. 

There is an ongoing trial testing this in humans now.  Seattle's own RCKC is a study site.

Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial

Gen Hosp Psychiatry. 2012 Aug 13
Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial.
Maldonado JR, Nguyen LH, Schader EM, Brooks JO 3rd
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine
PMID: 22898443

This was a randomized but open label trial comparing loading with long acting benzo (diazepam) to symptom triggered short acting benzo (lorazepam).


Over 12 months, 47 patients were randomized mostly at the Palo Alto VA but some at Stanford. 


Loading protocol (LP)

On day 1: Load with diazepam 20 mg by mouth every 2 h × 3 doses. (or diazepam 10 mg IV every 1 h × 6 doses). Hold for excessive sedation or RR<10.Additional diazepam 10 mg by mouth or intravenously may be administered every 2 h as needed for residual withdrawal symptoms (e.g., CIWA-Ar>8 or vital signs alteration suggestive of a hyperadrenergic state, such as SBP>140, DBP>90, HR>100). Hold for excessive sedation or RR<10.

Symptom-triggered protocol (STP)

Lorazepam 1 to 2 mg, by mouth or intravenously, may be administered every 2 h as needed for active withdrawal symptoms (e.g., CIWA-Ar>8 or vital signs alteration suggestive of a hyperadrenergic state, such as SBP>140, DBP>90, HR>100). Hold for excessive sedation or RR<10.RR=respiratory rate; SBP=systolic blood pressure; DBP=diastolic blood pressure; HR=heart rate.

There were no statistically significant differences although the diazepam loading protocol was marginally better with  69.6% symptom free at 72 hours vs 41.7% for the lorazepam symptom triggered protocol.  The average rate of CIWA improvment per day was -2.3 for the loading dose vs  -1.5 for the symptoms triggered.  Total diazepam 103 mg for the loading protocol and 92.4 mg diazepam equivalents (assuming 1 mg of lorazepam to 5 mg of diazepam) for the symptom triggered pts. 

Two patients, one in each group with DTs severe enough to require transfer to ICU.

This study conflates two questions, short vs long acting benzo and loading vs symptom triggered dosing.  The short answer is that it doesn't make much difference, or at least no statistically different difference. The slight edge to the loading protocol could be attributed to either the early dosing or the potential advantages of long acting benzo.

UK National Institute for Health and Clinical Excellence: Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence

England's NICE (National Institute for Health and Clinical Excellence) put out this guideline in February of 2011.   It gives a view of a national public health system addressing the problem of alcoholism.  The approaches seen here may be come more common in the US if health care reform leads to a more systematic cost sensitive approach.

The guideline is available at: http://www.nice.org.uk/nicemedia/live/13337/53191/53191.pdf.

The authors note a prevalence of alcohol dependence of 4% and harmful drinking of 25% in the UK.

For harmful drinking and mild dependence, behavioral approaches are recommended. The guideline suggests outpatient counseling, 60 minutes weekly for 12 weeks for most patients. More intensive outpt treatment is reserved for people "with moderate and severe alcohol dependence who have:  very limited social support (for example, they are living alone or have very little contact with family or friends) or complex physical or psychiatric comorbidities or [who have ] not responded to initial community-based interventions"

Residential rehabilitation is advised for the homeless but otherwise not much discussed. The benefit of residential vs community treatment is listed as a research questions.

Treatment with acamprosate or oral naltrexone is advised, with a course of 6 months.  The medication can be considered a failure if no improvement by 4-6 weeks.  Depot IM naltrexone is not mentioned, neither is topiramate. Disulfiram is mentioned as an option for motivated patients with family members to monitor use.  Concurrent counseling is advised. 

Outpatient withdrawal treatment is discussed. They advise patients be seen at least every other day.  Fixed or symptom triggered dose of chlordiazepoxide or diazepam is recommended, although no dosing regimen is given. Withdrawal treatment is expected to last 7-10 days. They advise family monitoring when possible. 

Inpatient withdrawal treatment is advised for patients drinking more than 30 units per day, hx of seizures or DTs, people with cardiovascular, hepatic  psychiatric comorbidities and for those on concurrent benzodiazepines.  

Benzodiazepine is expected to be treated inpt over 2-3 weeks or outpt over more than 3 weeks with tapering doses. Use of seizures medications is not discussed.