Open studies

Luttichau U, Arcangeli P, Sinapi S The use of rifaximin in the treatment of acute diarrhoeal enteritis Open study. Panminerva Med 1985 27 129-132. 

Fiorentino F, Simioli F, Conte M, Postiglione A, Cinque F, Santaniello A Open study on the antidiarrhoeal effectiveness of the L 105 compound. Chemioterapia 1984 3 132-135. 

Ena P, Zanetti S, Sechi L, Fadda G Open study on rifaximin topical treatment for skin infections due to pyogenic bacteria. NAM (Milan) 1993 9 325-328. 

An open study has also shown that 1 month s treatment of severe asthmatic patients with BN 52063 improves both FEV1 and inhibits eosinophil infiltration induced by PAF in the skin test [188]. In another study, severely asthmatic children were treated with the Ginkgo extract, GBE 761 (1 drop/kg three times a day). Complete recovery was observed in 60% of the children as determined by both clinical and spirometric (FEV1) parameters. Of the remainder, 30% showed moderate improvement and only 10% were resistant to therapy [ 188],... 

The planning of this type of investigation as an empirical, open study of responses must be carefully related to the nature and what is known of the product concerned. 

Wilson CG, Washington N, Greaves JL, Kamali F, Rees JA, Sempik AK, Lampard JF. Bimodal release of ibuprofen in a sustained-release formulation—a scintigraphic and pharmacokinetic open study in healthy volunteers under different conditions of food-intake. Int J Pharm 1989 50 155—161. 

Side effects In an open study with 3,250 subjects, the most common side effects reported were gastrointestinal irritation (0.6%), allergic reactions (0.5%), fatigue (0.4%), and restlessness (0.3%). 

Numerous open studies, and seven controlled studies, have shown that valproate is effective in the treatment of acute mania. It has also been claimed to have an antidepressant action. Recent studies have shown that valproate is effective in the long-term treatment of bipolar disorder. 

Other drugs that are reported to have beneficial effects but which have not undergone such extensive evaluation as the neuroleptics or carbamazepine include the calcium channel antagonists such as verapamil. A small open study has suggested that the alpha2 adrenoceptor agonist clonidine may... 

There is much controversy over the use of open or open-label studies. It is a golden rule of clinical trial design that, wherever practicable and possible, open studies should not be conducted, but there are circumstances when they can or must be used (see Box 6.2). 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

In 1992, an open study of 22 psychiatric inpatients, ages 5 to 12 years, with disruptive behavioral and mood disorders were treated with trazodone. The results revealed a significant decrease in aggressive and impulsive behaviors in 13 of the patients following therapy with trazodone (Zubieta and Alessi, 1992). 

Kusumakar, V. and Yatham, L.N. (1997) An open study of lamotrigine in refractory bipolar depression. Psychiatry Res 72 145-148. 

Semah, F, Gimenez, F, Longer, E., Laplane, D., Thuillier, A., and Baulac, M., (1994) Carbamazepine and its epoxide an open study of efficacy and side effects aftet catbamazepine dose incte-ment in refractory partial epilepsy. Ther Drug Monit 16 537-340. 

In open studies of adult ADHD, moderate improvements were reported in studies with pargyline and selegiline (MAOI-Bs) (Wender et ah, 1983, 1985). In a controlled study of selegiline in adult ADHD (Ernst 1996), use of active drug failed to produce results different from those with placebo however, the placebo response was unusually high in that study. In addition, a high dose (60 mg) was more effective than a low dose (20 mg), which suggests that MAOI-A effects may be more helpful in the treatment of ADHD. 

As may be expected, studies of antidepressants in treatment of ADHD have not shown a differential effect in ADHD children with or without conduct disorder, depression, or anxiety (Biederman et ah, 1993b). While DMI-treated ADHD children showed a substantial reduction in depressive symptoms compared with placebo-treated patients (Biederman et ah, 1989), DMI appears not to be as powerful an antidepressant in children as the SSRls. (Bostic et ah, 1999). The safety and efficacy of combined SSRl and stimulant pharmacotherapy has been addressed in two open studies and is currently being evaluated in a prospective study conducted by the Resarch Units in Pediatric Psychopharmacology (RUPP) Network (B. Vitiello, personal communication). 

The safety and efficacy of combined SSRI and stimulant pharmacotherapy have been addressed in two open studies. Gammon and Brown (1993) reported on the successful addition of fluoxetine to stimulants in the treatment of 32 patients with ADHD with comorbid depressive and anxiety disorders (Gammon and Brown 1993). These children with comorbid conditions had failed to respond to methylphenidate alone. Another report detailed the addition of methylphenidate to SSRI treatment (Findling, 1996). Depressed children and adults with comorbid ADHD were treated with either fluoxetine or sertraline. While depressive symptoms remitted, ADHD symptoms persisted. Methylphenidate was added and successfully treated the ADHD symptoms. In both investigations, the combined treatment was well tolerated. 

Most child and adolescent studies published thus far have focused on the effects of the tricyclic antidepressants (TCAs) and, more recently, the SSRIs. A few open studies have also shown that monoamine oxidase inhibitors (MAOIs) can be used safely with children and adolescents (Ryan et ah, 1988b), but noncompliance with dietary requirements may present a significant problem for minors. Other antidepressants, including the heterocyclics (HTC) (e.g., amoxapine, maprotiline), buproprion, venlafaxine, and nefazodone, have been found to be efficacious for the treatment of depressed adults (APA, 2000), but they have not been well studied for the treatment of MDD in children and adolescents. Therefore, this chapter mainly describes the use of SSRIs and TCAs for youth with MDD. 

The MAOIs have been found to be beneficial for patients who have not responded to other medications (Thase and Rush, 1997 APA, 2000). An open study suggested that adolescents with depression who did not respond to TCAs responded to MAOIs (Ryan et ah, 1988b). However, it is possible that these adolescents did not respond to TCAs because this group of medications is not efficacious for the treatment of pediatric MDD (Birmaher et ah, 1996a). 

In adolescents with MDD, an open study showed significant improvement of refractory depressive symptoms after augmentation of TCA treatment with lithium (Ryan et al., 1988a). Another open-label study did not replicate this finding (Strober et al., 1992). 

Hughes et ah, 1999 Plizka, 2000). This strategy has not been validated, however. Recently an open study using bupropion suggested that this medication can be efficacious to treat both MDD and ADHD (Daviss et ah, 2001), although its effect on ADHD is not as impressive as that obtained with stimulants (Conners et ah, 1996). 

Grunhaus, L., Dannon, P.N., and Schreiber, S. (2000) Repetitive trans-craneal magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder an open study. Biol Psychiatry 47 314-324. 

There are no randomized, double-blind, controlled studies of hospitalized children and adolescents with acute mania. Two systematic, albeit open, studies of lithium in hospitalized, acutely manic adolescents had response rates of 67%-80% in classic manic adolescents, and 33%-40% in manic adolescents with prior ADHD (Strober et al., 1988 1998). In a discontinuation study in which manic adolescents stabilized on lithium were subsequently assigned double-blind to placebo or continuation treatment, the response rate was 53.5%, and the presence of prior ADHD made no difference in outcome (Kafantaris et al., 1998). However, the presence of psychosis decreased the likelihood of lithium response and antipsychotic medication was necessary for stabilization. Naturalistic discontinuation of lithium (because of noncompliance) after stabilization resulted in relapse rates of 90% vs. 37.5% for those remaining on lithium (Strober et al., 1990). A NIMH multisite study is currently examining this issue more systematically. 

The extent of Buspirone experience in children and adolescents is limited to open studies and case reports. There are no published double-blind placebo-controlled studies of Buspirone for pediatric anxiety disorders or any other psychiatric disorder. Results of a recently completed large (n = 350 ages 6-17 years), industry-sponsored, multisite study of Buspirone for children (15-30 mg/day) and adolescents (45-60 mg/ day) with GAD have not been published or presented at open academic conferences. Until such data are made available, the use of Buspirone for treatment of pediatric anxiety disorders remains speculative. 

Despite the history of robust BZ anxiolytic impact in adults, controlled studies, open studies, and case reports of BZs for pediatric anxiety have not been impressive. Concerns about BZ-related adverse events, such as behavioral disihnhibition, have since slowed interest in controlled studies of BZs for treatment of pediatric anxiety disorders. Three small placebo-controlled studies of BZs for pediatric anxiety disorders have been published and none demonstrated... 

Available pharmacokinetic (PK) studies of medications with potential to treat pediatric anxiety disorders have been open studies that examine PK parameters and monitor adverse effects in children and adolescents. None of the pediatric PK studies described below were designed as dose finding studies, and none of the studies were able to describe a clear association between dose or exposure and specific adverse effect. However, pediatric PK data can be useful to guide dosing and adverse effect monitoring to the extent that the weight-adjusted PK parameters inform extrapolation based on comparable studies of adult PK. The following summary of PK studies is based on multiple-dose PK studies. 

Dursun, S.M., and Reveley, M.A. (1997) Differential effects of trans-dermal nicotine on microstructured analyses of tics in Tourette s syndrome an open study. Psycholo Med 27 483 87. 

Donovan et al. (1996, 1997) completed an open study evaluating the use of valproic acid (Depakote) in adolescent outpatients with marijuana abuse or dependence and explosive mood disorder (mood symptoms were not classified using the DSM FV Diagnostic System). Eight subjects were prescribed 1000 mg of valproic acid (Depakote) for 5 weeks, in addition to regular therapy sessions, but did not receive any other psychotropic medications. All subjects showed a significant improvement in their marijuana use (p <0.007) and their affective symptoms (p < 0.001), although both outcomes were measured only by self-report. The most common adverse events were nausea and sedation. No subjects discontinued because of these side effects, nor were there any reported interactions between the valproic acid (Depakote) and substances of abuse. 

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