Children with asthma have improved pulmonary functions after massage therapy

OBJECTIVE: Opioid withdrawal has been associated with poor fetal growth, preterm delivery, and fetal death. We sought to evaluate the safety of antepartum opioid detoxification in selected gravidas. METHODS: Between 1990 and 1996, women with singleton gestations who reported opioid use were offered inpatient detoxification. Predetoxification sonography was performed to confirm gestational age and to exclude fetuses with growth restriction and oligohydramnios. Women with mild withdrawal symptoms were given clonidine initially, and methadone was substituted if symptoms persisted. Objective signs of withdrawal were treated with methadone from the outset. Antenatal testing was performed once gestations reached 24 weeks. Newborns were observed for signs of neonatal abstinence syndrome and were treated as necessary. Obstetric and neonatal outcome data were collected. RESULTS: Thirty-four gravidas elected to undergo opioid detoxification at a mean gestational age of 24 weeks. The median maximum dose of methadone was 20 mg per day (range 10-85 mg), and the median time to detoxification was 12 days (range 3-39 days). Overall, 20 women (59%) successfully underwent detoxification and did not relapse, ten (29%) resumed antenatal opioid use, and four (12%) did not complete detoxification and opted for methadone maintenance. There was no evidence of fetal distress during detoxification, no fetal death, and no delivery before 36 weeks. Fifteen percent of neonates were treated for narcotic withdrawal. CONCLUSION: In selected patients, opioid detoxification can be accomplished safely during pregnancy.     

Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.     

A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence

BACKGROUND: Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance. METHODS: Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period. RESULTS: Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted. CONCLUSIONS: Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.     

The acceptability, safety, and tolerability of methadone/naloxone in a 50:1 ratio.

Methadone is an effective therapy for heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed methadone. Combination with naloxone is one way to reduce the risk of diversion and injection. Two studies were conducted. The first ascertained the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral methadone-naloxone in a 50:1 ratio compared with methadone. The second study investigated the effectiveness of intramuscularly injected methadone-naloxone in precipitating withdrawal in methadone-maintained subjects. The first double-blind, crossover study randomized 10 stable methadone-maintained subjects equally to receive either methadone-naloxone or methadone over two alternate 14 day periods. In the second study, 5 subjects received intramuscular injections of methadone-naloxone before their scheduled methadone dose. Oral methadone-naloxone in a 50:1 ratio appeared to be well tolerated, although a taste difference between the preparations may have compromised blinding. There were no significant differences between methadone and methadone-naloxone in objective and subjective opioid withdrawal signs, and trough and peak plasma concentrations. Methadone-naloxone in a 50:1 ratio intramuscularly precipitated mild to moderate signs of opioid withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience withdrawal at a lower dose refused higher dose challenges. Withdrawal symptoms peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60 minutes. Methadone-naloxone in 50:1 ratio has the pharmacological properties to be a useful combination product for treatment of heroin addiction with reduced risk of injection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Buprenorphine treatment of opioid dependence: A review.

Buprenorphine, a partial mu-agonist opioid, is a promising pharmacotherapy for the treatment of opioid dependence. One hundred and eight papers are organized according to 3 components essential to buprenorphine's use as a pharmacotherapy for opioid dependence: inducting patients onto buprenorphine, maintaining patients on buprenorphine, and discontinuing patients from buprenorphine treatment. The research suggests that inducting patients onto buprenorphine should lead to limited discomfort if appropriate procedures are followed. As a maintenance treatment, buprenorphine is as efficacious as methadone, blocks the effects of exogenously administered opioids, promotes treatment compliance, and, importantly, can support an alternate day dosing regimen by doubling the daily dose. Discontinuing buprenorphine treatment appears to result in a mild-to-moderate opioid withdrawal syndrome that is less severe than that observed with full-efficacy agonists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potential benefits of estrogens and progestogens on breast cancer

Comparatively few studies have examined the effects of methadone given during a clinical detoxification programme. Furthermore, their results are different especially because of changing drop-out rates. This study was carried out on a drug-detoxification ward and investigated the effects of methadone given to alleviate withdrawal symptoms. Comparisons were undertaken with patients withdrawn during a one-year period before methadone was available. No significant difference was found between drop-out rates of patients with methadone-supported detoxification (n = 113, drop-out rate: 41.6%) and patients who did not receive methadone during detoxification (n = 108, drop-out rate: 37.0%). Nevertheless the drop-out rate in the first three days of withdrawal was reduced from 15.7% to 8.0%. On average the critical drop-out moment shifted from 5.3 days to 10.1 days. Interpretations of these findings should take into account, that the number of patients who underwent a voluntary detoxification programme for the first time was nearly doubled after methadone was offered on the ward and, additionally, many more patients tried to withdraw from methadone taken within an outpatient methadone-maintenance programme.     

Diagnosis of pulmonary arteriovenous malformations by colour Doppler ultrasound and amplitude ultrasound angiography

STUDY OBJECTIVE: To evaluate the effect of ultra-rapid opioid detoxification on spontaneous respiration. DESIGN: Prospective study. SETTING: University of Illinois, Chicago, Hospital. PATIENTS: 20 ASA physical status I and II patients undergoing ultra-rapid opioid detoxification, and 5 ASA physical status I and II control patients undergoing surgical procedures. INTERVENTIONS: Ultra-rapid opioid detoxification patients were anesthetized with propofol, intubated, and spontaneously ventilating. Opioid detoxification was achieved by giving repeated increasing intragastric doses of naltrexone. Control patients were anesthetized with propofol and 70% nitrous oxide and were time-based controls for opioid detoxification. MEASUREMENTS AND MAIN RESULTS: Respiratory rate and minute ventilation were measured and increased 80% to 100% during opioid detoxification (p < 0.05). Respiratory rate and minute ventilation did not change in controls. Oxygen consumption and carbon dioxide (CO2) production were measured in separate studies and increased during ultra-rapid opioid detoxification with increases in spontaneous ventilation, but not when the patients were paralyzed. CONCLUSIONS: Spontaneous ventilation increases during opioid detoxification without a change in end-tidal CO2. An increase in metabolism is produced in opioid withdrawal that is mediated by elevated muscle activity.     

Early impact of methadone induction for heroin dependence: Differential effects of two dose sequences in a randomized controlled study.

The pharmacodynamic and pharmacokinetic effects of 2 methadone (METH) induction dose sequences were evaluated in this 15-day outpatient experimental protocol. Heroin-dependent, non-treatment-seeking volunteers were randomly assigned (stratified for gender, race, and route of heroin use) to 2 groups. In 1 sequence, METH doses ascended (28, 56, then 84 mg/day; stepwise, n = 18), whereas in the other sequence doses escalated, then tapered (28-84 mg on Days 1-6 to 56 mg/day; rapid, n = 16). A contingency-management intervention was common to both groups. Drug use and heroin craving and opioid withdrawal symptoms decreased, whereas agonist symptoms and positive mood increased overall across days for both groups. Plasma concentrations and the acute reinforcing effects of METH paralleled each dose sequence. Stepwise relative to rapid METH induction significantly decreased heroin craving and opioid withdrawal symptoms and increased agonist symptoms and positive mood but did not significantly improve drug use or retention. Although these specific dosing procedures would not necessarily be used in clinical settings, they provide a procedural template that might be applied safely and effectively with a broader range of treatment-seeking individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monounsaturated oils do not all have the same effect on plasma cholesterol

The relationship between pupil size and subjective symptoms of opiate withdrawal during gradual opiate agonist detoxification has not yet been studied. In the current study, the authors sought to determine the relationship between pupil size and intensity of opiate withdrawal symptoms. To accomplish this, they examined 19 subjects meeting DSM-IV criteria for opiate dependence (304.00) on agonist therapy. All subjects were undergoing opiate detoxification with either methadone or the longer-acting 1-alpha acetylmethadol (LAMM). During two separate visits, subjects' pupil sizes were assessed in the dark using a pupillometer. At each visit, subjects completed two standardized assessment tools (the Subjective Opiate Withdrawal Scale [SOWS] and the Weak Opiate Withdrawal Scale [WOWS]) for measuring subjective symptoms of opiate withdrawal. It was found that changes in pupil size significantly correlated with WOWS, but not with SOWS, scores. Larger pupil sizes were associated with less withdrawal distress. The sensitivity of the pupillometric test to detect increases in opiate craving during opiate agonist medication reduction was 92%, with a specificity of 57%. The predictive value of a positive test was 79%, whereas the predictive value of a negative test was 80%. Pupillometry may provide an objective measure of the intensity of opiate withdrawal in subjects during gradual methadone detoxification.     

Clonidine suppresses the opioid abstinence syndrome without clonidine-withdrawal symptoms: a blind inpatient study

Nine hospitalized opioid-addicted patients were blindly given clonidine within 36 hours of the abrupt and blind discontinuation of methadone. All nine patients were successfully withdrawn from methadone and were asymptomatic upon discharge. Clonidine-treated patients had significantly fewer symptoms than a comparable group of opioid addicts abruptly withdrawn from methadone. No exacerbation of symptomatology developed after the cessation of clonidine. The clinical implications of clonidine's suppression of opioid withdrawal and the alpha-2 adrenergic mediation of the abstinence syndrome are discussed.     

Heroin craving and drug use in opioid-maintained volunteers: Effects of methadone dose variations.

Recent data indicate that opioid agonist and antagonist challenges decrease and increase (respectively) heroin craving in physically dependent individuals. This study investigated effects of methadone dose variations on craving and new drug use in 18 outpatients who were given money contingencies. In Phase 1, volunteers were told in different test sessions that methadone dose would increase, decrease, or stay the same; drug-abstinence contingencies were suspended for 24 hr. Craving significantly increased and new heroin use marginally increased (relative to maintenance dose) only when a dose reduction was paired with a dose decrease instruction. In Phase 2 (detoxification), craving and heroin use significantly increased as methadone dose decreased. Thus, loss of μ-receptor agonist effect increased craving and risk of relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation of detoxification fear to methadone maintenance outcome: 5-year follow-up.

Assessed 5-yr treatment outcome follow-up on 56 methadone maintenance patients originally assessed for detoxification fear. Three fear measures (psychometric, interview, and self-report) were associated with treatment outcome variables by canonical correlation, representing 40% shared variance between predictor and predicted variables. Detoxification fear was associated with longer treatment, fewer treatment episodes, fewer methadone detoxification attempts, and fewer successful methadone detoxifications. Findings suggest that detoxification fear is a significant factor that may affect methadone maintenance outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparing Hatha yoga with dynamic group psychotherapy for enhancing methadone maintenance treatment: a randomized clinical trial

BACKGROUND: As more methadone treatment programs are funded in an attempt to curb substance abuse and HIV infection among i.v. drug users, more cost effective treatment approaches are being sought. OBJECTIVES: To investigate whether clients in outpatient methadone maintenance treatment who practice weekly Hatha yoga in a group setting experience more favorable treatment outcomes than those who receive conventional group psychodynamic therapy. METHODS: After a 5-day assessment period, 61 patients were randomly assigned to methadone maintenance enhanced by traditional group psychotherapy (ie, conventional methadone treatment) or an alternative Hatha yoga therapy (ie, alternative methadone treatment). Patients were followed for 6 months and evaluated on a variety of psychological, sociological, and biological measures. The revised Symptom Check List provided the primary psychological measures; the Addiction Severity Index provided various indices of addictive behaviors. RESULTS: The evidence revealed that there were no meaningful differences between traditional psychodynamic group therapy and Hatha yoga presented in a group setting. Both treatments contributed to a treatment regimen that significantly reduced drug use and criminal activities. Psychopathology at admission was significantly related to program participation regardless of treatment group. DISCUSSION: In addition to examining the characteristics of patients who present for treatment, this study identifies unexpected staff issues that complicate the integration of alternative and traditional treatment strategies. CONCLUSION: Alternative methadone treatment is not more effective than conventional methadone treatment, as originally hypothesized. However, some patients may benefit more from alternative methadone treatment than conventional methadone treatment. Additional research is necessary to determine characteristics that identify patients who might benefit from alternative methadone treatment.     

Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment.

Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J. S. Baer, C. S. Holt, and E. Lichtenstein (see record 1987-13846-001) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical pharmacology of buprenorphine: ceiling effects at high doses

OBJECTIVE: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial mu-agonist, across a wide range of doses in comparison to methadone. METHOD: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration. RESULTS: Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range. CONCLUSIONS: This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.     

Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B

PURPOSE: The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin. PATIENTS AND METHODS: Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17). RESULTS: No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001). CONCLUSION: Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.     

Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home

PURPOSE: The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. PATIENTS AND METHODS: A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. RESULTS: differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. CONCLUSION: Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.     

Repeated dosing with oral cocaine in humans: Assessment of direct effects, withdrawal, and pharmacokinetics.

Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1–4 & Days 9–12, cocaine 175 mg, p.o.; 5 hourly doses; 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5–8). After these 12 days, an additional period of 28 days of placebo maintenance followed (Days 13–40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The dosing regimen produced cocaine plasma concentrations (Cmax of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high doses of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opiate dependence, comorbidity and seasonality of birth

OBJECTIVE: In contrast with the non-opiate dependent population, persons biologically-dependent upon opioids display an excess life-time prevalence of affective and anxiety disorders. Many of these addicts state that opiates, particularly methadone, relieve or diminish the severity of their dysphoria. The purpose of this study is to explore this phenomena by analyzing how a specific population of long-term addicts (mean years of addiction 16.9, SD 3.8) differs from a non-opiate dependent population regarding seasonality of birth. METHODS: Birth months were determined for 457 opiate dependent patients, placed onto methadone maintenance for intractable opiate dependence, born between 1930-1970 (sorted by sex, race, year and place of birth), and compared to normal US birth statistics. Affective and anxiety disorders were screened for using psychometric testing, verified by structured clinical intervals. RESULTS: A significant difference was noted when comparing monthly births rates for patients and normals. Grouping the monthly data into birth trimesters (Oct-Jan; Feb-May; Jun-Sep) clearly shows this difference: opioid dependent persons--38.5/29.8/31.8%; normals--33.4/32.0/34.7%. As a group, intractable, opioid dependent patients demonstrate an increased life-time prevalence, relative to normals, of anxiety (27.8 vs. 13.9%), dysthymia (23.4 vs. 6.4%) and combined anxiety + dysthymia (17.9 vs. 1.5%); opioid dependent persons born between Oct-Jan demonstrated more anxiety (32.0 vs. 25.1%), dysthymia (29.3 vs. 19.5) and combined anx + dys (23.3 vs. 14.4) than those born in the other two trimesters. CONCLUSION: Persons entering methadone maintenance for opiate dependence with comorbid anxiety, dysthymia or combined anxiety + dysthymia are more likely to have been born in the period of Oct-Jan. This may be due to a higher risk of developmental aberrations occurring in infants born during the light-limited portion of the year creating a later propensity for intractable, opiate dependence.