Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients

• INCLUSION CRITERIA:

  1. Age between 18 and 60
  2. Evidence of physical dependence on opioids (self-report, urine screen, physical exam)
  3. Seeking treatment for opioid dependence
  4. Able to attend treatment clinic 7 days/week

EXCLUSION CRITERIA:

General-

1. Poor venous access
2. Urologic conditions that would inhibit urine collection
3. Pregnancy or breastfeeding
4. Failure to agree to use a medically effective form of contraception while in the study (in women who are sexually active with a male partner and able to get pregnant). Acceptable forms of contraception for this study include: hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), surgical sterility (tubal ligation or hysterectomy); IUD; Diaphragm with spermicide; Condom with spermicide
5. Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines

Psychiatric-

1. Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires (Shipley Institute of Living scale estimated full-scale IQ less than 80)
2. History of schizophrenia or any other DSM-IV psychotic disorder
3. History of bipolar disorder
4. Current Major Depressive Disorder

Medical-

1. Any active or untreated medical illness that in the view of the investigators would compromise participation in research
2. Allergy or intolerance to either buprenorphine or clonidine
3. Cerebrovascular disease
4. Conduction disturbances (e.g., second-degree heart block, third-degree heart block, atrial fibrillation, ventricular tachycardia) or arrhythmias
5. Myocardial infarction, or documented coronary artery disease
6. Congestive heart failure
7. Chronic renal failure, as estimated by Cr > 2.0
8. CD4 < 200 or evidence of severely compromised immune system /AIDS
9. Marked, sustained bradycardia (HR < 45 bpm) on three separate occasions
10. Marked, sustained low blood pressure (SBP <95 or DBP < 40 mm Hg) over three separate readings
11. Marked, sustained high blood pressure (SBP >160 mm Hg, DBP >100 mm Hg) over several readings, without being on antihypertensive medications.
12. ECG changes suggestive of acute ischemia, clinical important arrhythmia, left bundle branch block, or other changes that concerns the MRP will exclude the participant. If accompanied by cardiovascular complaints such as chest pain or syncope, less specific ECG findings will also exclude the patient. When in doubt, the ECG will be sent to cardiology on a prn basis for a manual reading.
13. Orthostatic hypotension (upon standing for 3 minutes, there is a 20 mm Hg decrease in systolic blood pressure or a 10 mmHg decrease in diastolic blood pressure accompanied by an increase by 20 bpm in heart rate) on two separate readings.

Taking contraindicated medications-

1. Beta blockers
2. Tricyclic antidepressants
3. Antipsychotics
4. Mah huang
5. Yohimbe
6. Ephedra
7. Sildenafil citrate (Viagra). Sildenafil citrate doses > 25mg should not be taken within 4 hours of taking an alpha blocker or it can produce significant and symptomatic hypotension (Pfizer). Of note, Viagra, like buprenorphine, is metabolized by cytochrome P450 3A4. Ingestion of buprenorphine could potentate the effects of sildenafil citrate which could extent the period of safety to > 4 hrs from when an alpha blocker could be taken after Viagra ingestion.

Family history of sudden cardiac death at age < 50

Lab Test and Lab Values:

WBC* < 1,500 > 13,000 #/CUMM

HCT < 33 > 49 Percent

Platelets < 100 > 500 K/CUMM

Sodium < 132 > 149 MEQ/L

Potassium < 3.5 > 5.2 MEQ/L

Calcium < 8.4 > 10.5 MG/DL

Magnesium < 1.3 > 3 MG/DL

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BUN > 35 MG/DL

Cr<TAB> > 2.0 MG/DL

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Alk Phos<TAB> > 200 U/L

AST<TAB> > 200 U/L

ALT<TAB> > 200 U/L

GGT<TAB> > 400 U/L

Albumin<TAB> < 3 GM/DL

Total bilirubin > 2.0 MG/DL

Direct bilirubin > 0.4 MG/DL

TSH<TAB> < 0.27 > 4.2 UIU/ML

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*Leukocytosis will prompt further investigation before clearance.<TAB>