The primary objective of this study was to determine if the abuse liability of methylphenidate is governed by formulation differences that affect rates of drug delivery. In this double-blind, placebo-controlled, randomized, crossover study, subjects with a history of recreational drug use received single oral doses of placebo, 60 mg of immediate-release methylphenidate (IR) and 108 mg of extended-release methylphenidate (osmotic release oral system [OROS]). Over 24 hours after dosing, blood was collected to determine plasma concentrations of methylphenidate, and subjects completed subjective assessments of abuse liability (Addiction Research Center Inventory, Drug Rating Questionnaire-Subject, and Subjective Drug Value). The abuse-related subjective effects of IR and OROS methylphenidate were statistically significantly different from placebo, confirming the overall validity of the study. Although a higher dose of OROS methylphenidate was used compared with IR methylphenidate (108 mg vs 60 mg), subjective effects were consistently lower for OROS compared with IR methylphenidate (statistically significant for 3 of 6 measures of positive effects), particularly at early time points. In general, pharmacokinetic-pharmacodynamic parameters were correlated from a poor to modest degree, with greater correlations observed for IR methylphenidate. In addition, a post hoc "qualification" method was developed, which demonstrated that pharmacological qualification might improve the assessment of subjective effects. Although requiring epidemiological confirmation, the results suggest that OROS methylphenidate, with its characteristic slow ascending plasma concentration profile, may have lower abuse potential. This conclusion is reflected by lower subjective responses during early hours as compared with the IR formulation with its rapid drug delivery and accompanying greater subjective effects.

Objective: The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate.Method: Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C-max) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography.Results: Despite similar C-max values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate.Conclusions: The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.

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OBJECTIVE To examine the potential for drug-drug interactions to influence drug metabolism between the attention-deficit/hyperactivity disorder (ADHD) dl-methylphenidate and atomoxetine with dextromethorphan, a probe for interactions involving cytochrome P450 (CYP) 2D6 isoenzyme. DESIGN In vitro and ex vivo analysis of changes in metabolism of study drugs. SETTING Laboratory. PATIENTS Not applicable. INTERVENTIONS Pooled human liver microsomal fractions prepared at CEDRA Corporation (now CellzDirect, Austin, Tex.) by the standard differential centrifugation method (lot 821-1). Human liver microsomes were pooled from 15 donors. Recombinant CYP 2D6-containing microsomes (Supersomes; lots 20 and 24 BD Gentest; Woburn, Mass.) were prepared from a baculovirus-infected insect cell line that expressed only the human CYP 2D6 isoform. Dextromethorphan, with and without effector, was incubated with pooled human liver and recombinant CYP 2D6-containing microsomes. Atomoxetine and dl-methylphenidate were tested at 0.1x, 1x, and 10x their reported therapeutic concentrations. Paroxetine, a known inhibitor of CYP 2D6, was used as a reference agent, and quinidine was used as a positive control inhibitor of CYP 2D6. MAIN OUTCOME MEASURES Changes in substrate metabolism indicative of CYP 2D6-mediated interactions. RESULTS Atomoxetine and paroxetine inhibited the formation of dextrorphan by about 50% in human liver microsomes and by more than 80% in recombinant microsomes; the profiles of atomoxetine and the known 2D6 inhibitor paroxetine were similar. High concentrations of dextromethorphan reversed the inhibition of its metabolism, indicating a competitive mechanism of the interaction. Conversely, dextromethorphan and dextrorphan only modestly inhibited atomoxetine and paroxetine metabolism. dl-Methylphenidate did not inhibit dextrorphan formation in either microsome preparation, and dl-methylphenidate metabolism was unaffected by dextromethorphan or dextrorphan. CONCLUSION These results demonstrate the potential for in vivo interactions between dextromethorphan and atomoxetine in patients with ADHD. However, they do not support the plausibility of an in vivo interaction between dextromethorphan and dl-methylphenidate.

The Formal Observation of Concerta versUs Strattera (FOCUS) study was conducted to assess, in children with ADHD, treatment outcomes with Concerta [OROS methylphenidate (MPH)], a once-daily controlled-release medication, and Strattera, (atomoxetine), a selective noradrenaline reuptake inhibitor, Because of the lack of data in minority groups treated for ADHD, the present subgroup analysis was conducted to determine the effectiveness and tolerability of ADHD treatments in African-American patients who were randomized to OROS MPH (n=125) or atomoxetine (n=58) during the FOCUS study. At the end of the study, the mean dose of OROS MPH was 32.8 +/- 10.9 mg and that of atomoxetine was 1.1 +/- 0.4 mg/kg. The results demonstrated that both treatments were associated with significant improvements in ADHD symptoms from baseline; however, patients who received OROS MPH demonstrated significantly greater improvements in total ADHD symptoms, inattentiveness and global improvement. The incidence of adverse events was similar in both treatment groups. OROS MPH and atomoxetine are effective and tolerable in the treatment of African Americans with ADHD, and significantly greater treatment responses were observed in patients receiving OROS MPH compared with those receiving atomoxetine over three weeks. Additional studies are needed to evaluate treatment response in this population.

The major human metabolite of atomoxetine (4-hydroxyatomoxetine) was tested against a panel of receptors and enzymes, and was found to interact with the mu, delta, and kappa-opioid receptors based upon studies involving both binding and functional assays. 4-hydroxyatomoxetine was determined to be a partial agonist of the kappa-opioid receptor.

Gastrointestinal complaints are common in infants and children and can result from the reflux of stomach contents into the esophagus. Although the therapeutic management of these symptoms involves both nonpharmacologic and pharmacologic interventions, very few treatments have been designed specifically for a pediatric population. This report summarizes various therapeutic options for treating common gastrointestinal conditions and symptoms in pediatric patients. In addition, preliminary results are presented for a multicenter, open-label study of a new pediatric antacid preparation. We gave 321 children from 2–11 years old Children's MYLANTA Upset Stomach Relief to treat complaints of upset stomach associated with acid indigestion, sour stomach or heartburn, or overindulgence of food and drink during a 2-week period. The product was associated with high rates of effectiveness and acceptance by physicians, parents, and children. Children experienced substantial relief of their gastrointestinal symptoms within 1 hour of taking this new antacid, as evidenced by the large changes in symptom ratings that were performed before and after dosing. An extraordinary 95% of the physicians' ratings and 92% of the parents' ratings of the overall effectiveness of the medication were “excellent” or “good.” The pediatric antacid preparation was very well tolerated, with fewer than 5% of the children reporting side effects that could be considered at least possibly related to the medication. Thus, these preliminary results indicate that Children's MYLANTA Upset Stomach Relief-the first antacid specifically formulated for pediatric use—is well tolerated and highly effective in relieving common gastrointestinal symptoms in both young and older children.

This randomized, double-blind, placebo-controlled, four-way crossover trial was designed to compare the efficacy of famotidine and placebo in preventing meal-provoked upper gastrointestinal symptoms. One hundred twenty-one subjects (58 men and 63 women), aged 20--61 years, were randomly assigned to one of four treatment sequences which included single oral doses of placebo, famotidine 5 mg, famotidine 10 mg, and famotidine 20 mg, spaced approximately 7 days apart. To be eligible for randomization, subjects had to have at least a 2-month history of heartburn and acid/sour stomach occurring at least three times per week. Treatment was administered 1 h prior to ingestion of test meals (chili and wine). Rescue antacid medication (Maalox((R))) was available for subjects who required additional relief. Heartburn severity. acid/sour stomach, and overall discomfort were evaluated on a six-point scale immediately prior to each test meal and every 15 min thereafter for 5 h. A global evaluation of the test medication, using a five-point scale, was performed prior to rescue medication use or at the end of each treatment session. Heartburn and peak acid/sour stomach were rated as significantly milder following prophylactic treatment with famotidine 5, 10, and 20 mg compared to placebo. Treatment with all three doses of famotidine was rated as "good" or "excellent" by significantly more subjects (58--63%) than following treatment with placebo (38%). In addition, rescue medication was used by significantly fewer subjects following famotidine (17--18%) compared to placebo (37%). Famotidine was generally well tolerated in this trial, with type and frequency of reported adverse experiences similar to that observed following placebo. These results indicated that famotidine doses of 5, 10, and 20 mg were significantly more effective than placebo in preventing symptoms of upper gastrointestinal distress when administered 1 h in advance of meal provocation.

Back to table of contents Previous article Next article ArticleNo AccessHeterogeneity of PTSDLAWRENCE C. KOLBLAWRENCE C. KOLBSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.146.6.811-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Heterogeneity of PTSD." American Journal of Psychiatry, 146(6), pp. 811-a–812 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byUnity or Anarchy? A Historical Search for the Psychological Consequences of Psychotrauma23 February 2023 | Review of General Psychology, Vol. 47Depression and Anxiety, Vol. 28, No. 9Posttraumatic Relationship Syndrome24 July 2016 | Clinical Case Studies, Vol. 5, No. 3A Jacksonian and Biopsychosocial Hypothesis Concerning Borderline and Related Phenomena17 November 2016 | Australian & New Zealand Journal of Psychiatry, Vol. 33, No. 6General Hospital Psychiatry, Vol. 20, No. 4Comment17 November 2016 | Australian & New Zealand Journal of Psychiatry, Vol. 31, No. 2An Integrative Two-Factor Model of Post-Traumatic StressComplex PTSDMedical Journal of Australia, Vol. 160, No. 3Journal of Traumatic Stress, Vol. 5, No. 3 Volume 146Issue 6 June 1989Pages 811-a-812 Metrics PDF download History Published online 1 April 2006 Published in print 1 June 1989

Back to table of contents Previous article Next article ArticleNo AccessDr. Ciccone and Associates ReplyPATRICK E. CICCONE, ALAN BURSTEIN, and ROBERT A. GREENSTEINPATRICK E. CICCONESearch for more papers by this author, ALAN BURSTEINSearch for more papers by this author, and ROBERT A. GREENSTEINSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.146.6.812AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Dr. Ciccone and Associates Reply." American Journal of Psychiatry, 146(6), p. 812 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByGeneral Hospital Psychiatry, Vol. 20, No. 4Biological Approaches to the Diagnosis and Treatment of Post-Traumatic Stress DisorderJournal of Traumatic Stress, Vol. 4, No. 1 Volume 146Issue 6 June 1989Pages 812-812 Metrics PDF download History Published online 1 April 2006 Published in print 1 June 1989

Back to table of contents Previous article Next article ArticleNo AccessDifferences Among Patients With PTSDPATRICK E. CICCONE, ALLAN BURSTEIN, and ROBERT A. GREENSTEINPATRICK E. CICCONESearch for more papers by this author, ALLAN BURSTEINSearch for more papers by this author, and ROBERT A. GREENSTEINSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.145.5.655-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Differences Among Patients With PTSD." American Journal of Psychiatry, 145(5), pp. 655-a–656 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByBehavior Therapy, Vol. 25, No. 2Dr. Moran and Associates ReplyMICHAEL G. MORAN, TROY L. THOMPSONII, and ALAN S. NIES1 April 2006 | American Journal of Psychiatry, Vol. 146, No. 6Dr. Ciccone and Associates ReplyPATRICK E. CICCONE, ALAN BURSTEIN, and ROBERT A. GREENSTEIN1 April 2006 | American Journal of Psychiatry, Vol. 146, No. 6Prodromal Symptoms in Agoraphobia and Panic DisorderDONALD F. KLEIN1 April 2006 | American Journal of Psychiatry, Vol. 146, No. 6Heterogeneity of PTSD23 January 2015 | American Journal of Psychiatry, Vol. 146, No. 6Prodromal symptoms in agoraphobia and panic disorder23 January 2015 | American Journal of Psychiatry, Vol. 146, No. 6 Volume 145Issue 5 May 1988Pages 655-a-656 Metrics PDF download History Published online 1 April 2006 Published in print 1 May 1988

Many types of external trauma have been linked to the genesis of posttraumatic stress disorder (PTSD) and yet recent reports have focused almost exclusively on PTSD occurring in the Vietnam veteran (PTSD/veteran). The extent to which treatment experiences with PTSD/veteran can be generalized to other traumatized patients, for example, acute civilian populations, has not been investigated. Clinical observations comparing PTSD precipitated by a motor vehicle accident with PTSD/veteran suggested there were major differences between these two groups on the following variables: source of referral, age, sex, socioeconomic level, nature of stressor, timing of the stressor, character of the intrusive and avoidance symptoms, and treatment noncompliance behavior. These differences were of sufficient magnitude to call into question the feasibility, at this time, of constructing generalizations regarding PTSD utilizing only the PTSD/veteran population.

Psychotropic agents are frequently utilized in the detoxification and maintenance of opiate addicts as well as in the treatment of their underlying psychopathology. Review of reports of studies conducted to data indicates that schizophrenia, depression, and anxiety in opiate addicts appear to respond to appropriate treatment with psychotropic drugs. Although nonaddictive psychoactive compounds cannnot be completely substituted for methadone in detoxification, their effects on the rate of methadone withdrawal warrant further study. To evaluate the results of treatment of addicts with psychoactive compounds, parameters that should be studied include the effects of these compounds on illicit drug use, methadone requirements, relapse and dropout rates, and social behavior.