Management of Functional Abdominal Pain.

Saito YA, Fox JC.

Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA saito.yuri mayo.edu

The diagnosis of functional abdominal pain should be made based on the Rome II symptom criteria with only limited testing to exclude other disease. During physical examination the clinician may look for evidence of pain behavior which would be supportive of the diagnosis. Reassurance and proper education regarding the clinical entity of functional abdominal pain is critical for successful treatment and good patient satisfaction. Education should include validation that symptoms are real, and that other individuals experience similar symptoms. No further treatment may be required for those with mild symptoms. For patients with more severe symptoms, a long-term management plan of either pharmacological or psychological treatments is warranted. This will require a commitment by both the patient and the physician to engage in a partnership with active involvement and responsibility by both individuals. The goal of treatment--to decrease pain and increase function over time, not to cure the disorder-- should be explained. Strong consideration should be made for the use of an antidepressant to treat analgesic effects. Tricyclic antidepressants are the mainstay of therapy for functional pain disorders. The analgesic effect is generally quicker in onset and occurs at a lower dose than their effect on mood. To maximize patient compliance, patients should be told the rationale behind their use, warned of the potential side effects, and reassured that many of the side effects will disappear with time. Choice of an antidepressant should be based on the presence of concomitant symptoms (eg, depression), cost, and physician familiarity with specific agents. All patients with functional abdominal pain should be screened for underlying psychiatric disturbance as an untreated mood disorder will adversely affect response to treatment. If a concurrent mood disorder is found, it should be treated by either using a higher dose of the tricyclic antidepressant or by adding another antidepressant agent. Psychological interventions such as cognitive behavioral therapy may be important as adjuvant therapy or as an alternative to treatment with antidepressants for those patients who find antidepressants ineffective or are intolerant to them. Narcotics and benzodiazepines should not be used to treat chronic abdominal pain due to the high risk of physical and psychological dependence.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15238203&dopt=Abstract antidepressant




Antidepressants and the risk of suicidal behaviors.

Jick H, Kaye JA, Jick SS.

Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Mass 02421, USA. hjick bu.edu

CONTEXT: The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. OBJECTIVE: To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. DESIGN AND SETTING: Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. PARTICIPANTS: The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). MAIN OUTCOME MEASURES: Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. RESULTS: After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide. CONCLUSIONS: The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.

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The antidepressant activity of Hypericum perforatum L. measured by two experimental methods on mice.

Bach-Rojecky L, Kalodjera Z, Samarzija I.

Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia. lbach pharma.hr

The pharmacological approach to the treatment of depression includes a long-term employment of antidepressants, either in the form of monotherapy or as a combination of several antidepressants with various mechanisms of action. Hypericum perforatum L. (St. John's wort) is the only natural antidepressant. Several constituents of the extract, such as hypericin and hyperforin, seem to be important for this effect. H. perforatum is considered to be an effective alternative to other therapeutic agents in the treatment of mild to moderate depression. The paper describes the investigation of the antidepressant effect of H. perforatum (doses 7, 35 and 70 mg kg(-1) b. m.) on mice using the forced-swimming and tail-suspension methods. As an indicator of the antidepressant effect, it was shown that the immobility time of animals in the forced-swimming and tail-suspension experiments was shorter, i.e. the activity of the animals was higher. With single doses of extract suspension increasing from 7 over 35 to 70 mg kg(-1) the antidepressant effect increased in proportion by 10.1%, 25.8% and 38.6% in the swimming method, and by 12.7%, 16.5% and 24.5% in the tail-suspension method compared to controls. H. perforatum extract displays dose-dependent antidepressant effect at a dose as low as 7 mg kg(-1). Both models have proved to be equally valuable for demonstration of substances with a potential antidepressant effect.

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Age effects on antidepressant-induced manic conversion.

Martin A, Young C, Leckman JF, Mukonoweshuro C, Rosenheck R, Leslie D.

Child Study Center, the Department of Psychiatry, Yale University School of Medicine, New Haven, CN 06520-7900, USA. Andres.Martin Yale.Edu

BACKGROUND: Antidepressant drug therapy can precipitate mania in vulnerable individuals, but little is known about the effects of age on this phenomenon. OBJECTIVE: To pharmacoepidemiologically evaluate the risk of conversion to mania by antidepressant class and patient age. DESIGN, SETTING, AND PATIENTS: Using an administrative national database of more than 7 million privately insured individuals, linked outpatient and pharmacy claims were analyzed for mental health users aged 5 to 29 years (N = 87,920). MAIN OUTCOME MEASURES: The proportion and cumulative hazard of manic conversion were analyzed by antidepressant class and subject age among children, adolescents, and young adults with an anxiety or nonbipolar mood disorder in the United States between January 1, 1997, and December 31, 2001. Manic conversion was defined as a new diagnosis of bipolar illness. RESULTS: During median follow-up of 41 weeks (range, 8-251 weeks), manic conversion occurred in 4786 patients (5.4%). Multivariate analyses using time-dependent Cox proportional hazards models indicated that an increased risk of manic conversion was associated with antidepressant category vs no antidepressant exposure (hazard ratios: 2.1 for selective serotonin reuptake inhibitors, P<.001; 3.8 for "other" antidepressants, P<.001; and 3.9 for tricyclic antidepressants, P =.002). Antidepressant x age interactions revealed inverse age effects for selective serotonin reuptake inhibitors and other antidepressants (beta = -.05; P<.001 for both) but not for tricyclic antidepressants (beta = -.02; P =.25). Peripubertal children exposed to antidepressants were at highest risk of conversion (number needed to harm: 10 [95% confidence interval, 9-12] among 10- to 14-year-olds vs 23 [95% confidence interval, 21-25] among 15- to 29-year-olds). CONCLUSIONS: Patient age is an effect modifier on the risk of antidepressant-associated manic conversion. Treatment with antidepressants is associated with highest conversion hazards among children aged 10 to 14 years.

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Trends in the use of antidepressants in a national sample of commercially insured pediatric patients, 1998 to 2002.

Delate T, Gelenberg AJ, Simmons VA, Motheral BR.

Express Scripts, Inc, Maryland Heights, Missouri 63043, USA. tdelate express-scripts.com

OBJECTIVE: The aim of this study was to estimate the prevalence of use of prescription antidepressants among children and adolescents by using nationwide data and to examine trends in use from 1998 to 2002. METHODS: Ambulatory prescription claims data for a nationwide random sample of more than 1.9 million life-years of commercially insured children (aged 18 years or younger) for the years 1998, 1999, 2000, 2001, and 2002 were examined retrospectively. The main outcome measure was trend in prevalence of antidepressant use. RESULTS: The overall prevalence of antidepressant use among children increased from 160 per 10000 (1.6 percent) in 1998 to 240 per 10000 (2.4 percent) in 2002, for an adjusted annual increase of 9.2 percent. The growth in the overall prevalence of antidepressant use was greater among girls (a 68 percent increase) than boys (a 34 percent increase). In 2002, antidepressant use was highest among girls aged 15 to 18 years, at 640 per 10000 (6.4 percent). The trend of increasing overall use of antidepressants among children and adolescents appears to have been driven primarily by greater use of selective serotonin reuptake inhibitors. CONCLUSIONS: The growth in the prevalence of use of antidepressant medications among youths appears to be continuing, and the rate of increase between 1998 and 2002 is similar to the rate of increase seen in the period of the second-generation antidepressants (late 1980s to mid-1990s).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15067149&dopt=Abstract antidepressant




Examining the adequacy of quantities available for subsidized antidepressant prescriptions in Australia.

McManus P, Mant A, Birkett D, Hemming M, Lindner J.

Drug Utilization Sub-Committee, Department of Health & Aged Care, Canberra, Australia.

In Australia the Pharmaceutical Benefits Scheme (PBS), a national drug insurance plan, aims to provide around a month's therapy for medication used in chronic conditions. However, there are marked differences among the most commonly used antidepressants in the number of days supply represented by the PBS maximum quantity after adjustment for the defined daily dose (DDD). The DDD is the assumed adult daily dose for a drug and is a WHO drug utilization standard. Whereas the selective serotonin re-uptake inhibitors (SSRIs) and moclobemide largely provide around a month's supply at the DDD, most tricyclic antidepressant (TCA) items provide considerably less than this .A patient tracking study was conducted to determine the average length of time between prescription re-supplies for a number of tricyclic antidepressants and newer antidepressants as a means of measuring the efficiency of PBS supply for the different classes of antidepressant. The number of days between dispensings was similar for patients no matter whether they were taking TCAs, SSRIs or moclobemide, although for the older antidepressants presumably at a much lower prescribed daily dose than the DDD.Care needs to be taken when adjusting usage with the DDD/1000/day unit of measurement in cases where the DDD does not reflect the prescribed daily dose (PDD). Copyright 1999 John Wiley & Sons, Ltd.

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Cholesterol-lowering drugs and antidepressants--a study of prescription symmetry.

Lindberg G, Hallas J.

The NEPI Foundation, Malmo University Hospital, Malmo, Sweden. Gunnar.Lindberg nepi.a.se

The subject of this study was to investigate the relationship between prescription of cholesterol-lowering drugs and depression. We used prescription of antidepressants as a proxy for depression and analysed the prescription order for cholesterol-lowering and antidepressant drugs. The ratio of persons with antidepressants prescribed second and first translates directly into a rate ratio (RR) associating cholesterol-lowering drugs use with antidepressants. The crude RRs were then adjusted for trends in sales of the drugs over the study period. All residents of Funen, Denmark, who started the two therapies during the period 1 April 1991 through 31 December 1995 were included in the study cohort. Of 184 individuals included in the analysis, 105 started antidepressant first and 79 second, giving a crude RR of 0.75. However, the sales of cholesterol-lowering drugs increased more than the sales of antidepressants. Accordingly, the adjusted RR was higher than the crude, 0.90 (95% confidence interval 0.68 to 1.22). Among three tested cholesterol-lowering drug classes, only simvastatin showed an adjusted RR above unity (1.59, 95% confidence interval 1.08 to 2.45). The hypothesis that the use of cholesterol-lowering drugs has an adverse effect on mood is not supported by the present study. Confounding by indication might explain the apparent association between use of simvastatin and antidepressants. Copyright 1998 John Wiley & Sons, Ltd.

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Antidepressant use and resource utilization in the general practitioner setting in The Netherlands.

Pathiyal A, Hylan TR, Quik R, Jones JK.

The Degge Group Ltd., Arlington, VA 22209-3109, USA.

OBJECTIVE: To assess antidepressant use and resource utilization in the general practitioner (GP) setting in the Netherlands following initiation of antidepressant therapy. DESIGN: Longitudinal study in a retrospective database. PARTICIPANTS: Sample of 869 patients from a new database in the Netherlands who initiated therapy on a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA). MAIN OUTCOME MEASURES: Mean length of antidepressant therapy within the first 90 days and resource utilization in the GP setting in the first 180 days following therapy initiation. RESULTS: (1) patients who initiated therapy on an SSRI were younger (48.6 years old versus 54.1 years old, p<0.01) and more likely to have a depression diagnosis (58% versus 30%, p<0.01) than patients who initiated therapy on a TCA; (2) patients who initiated therapy on an SSRI were more likely than patients who initiated therapy on a TCA (65% versus 52%, p<0.01) to have more than 30 days of therapy within the first 90 days and to receive antidepressant doses consistent with Dutch guidelines; (3) patients with greater than 30 days of antidepressant therapy within the first 90 days had more general practitioner visits than patients with 30 days of therapy or less (TCA patients: 9.6 versus 7.0; SSRI patients: 8.8 versus 6.9, p<0.01). CONCLUSIONS: Patients in the GP setting in the Netherlands who initiate therapy on SSRIs are more likely than patients who initiate therapy on TCAs to receive recommended doses and duration of therapy consistent with Dutch antidepressant treatment guidelines. Copyright 1998 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15073987&dopt=Abstract antidepressant