Open-label trial

Dorfman D, Dalton A et al (1999) Treatment of painful distal sensory polyneuropathy in HIV-infected patients with a topical agent results of an open-label trial of 5% lidocaine gel. AIDS 13(12) 1589-1590... 

Ferrando et al. (1999) conducted an open-label trial of fluoxetine or sertraline in 30 depressed HIV-positive women (including 16 of Puerto Rican or Dominican descent). No differences in treatment response or adverse effects were found between groups. 

Finally, a single open label trial of bupropion, a novel antidepressant with an obscure mechanism, found it helpful for depressive symptoms in PTSD patients but largely ineffective for the core symptoms of PTSD itself. 

Ormiston J, Serruys PW, Regar E, et al. A bioabsorb-able everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB) a prospective open-label trial. Lancet 2008 371 899-907. 

Adler, L., Resnick, S., Kunz, M. and Devinsky, O. (1995) Open-label trial of venlafaxine in attention deficit disorder. In New Clinical... 

Frazier, J.A., Biederman, J., Tohen, M., Feldman, P.D., Jacobs, T.G., Toma, V., Rater, M.A., Tarazl, R.A., Kim, G.S., Garfield, S.B., Sohma, M., Gonzalez-Heydrlch, J., Rlsser, R.C., and Nowlin, ZM (2001) A prospective open-label trial of olanzapine monotherapy in children and adolescents with bipolar disorder. / Child Adolesc Psychoparmacol 11 239-250. 

Como, P.G. and Kurlan, R. (1991) An open-label trial of fluoxetine for obsessive-compulsive disorder in Gilles de la Tourette s Syndrome. Neurology 41 872-874. 

The natural fluctuations of tics and the occasional improvement of tics on placebo mandate caution in interpreting open-label trials and anecdotal reports of alternative treatments. For example, a 12-week doubleblind, placebo-controlled study of clonidine found that in the placebo group (who also received the usual supportive care and regular contact with the treating clinicians), tic severity, as rated independently by parents, patient, and clinicians, improved 11%-13%. Other placebo-controlled studies report placebo response rates on the order of 6%-ll% (Gilbert et ah, 2000) (Sallee et ah, 2000b Scahill et ah, submitted). 

Fluphenazine, a typical neuroleptic of the phenothi-azine class, has been less widely used for treatment of tics than haloperidol or pimozide. A controlled trial of haloperidol, fluphenazine, and trifluoperazine found comparable tic-reducing efficacy, but greater sedation and extrapyramidal side effects for haloperidol fluphenazine was the best tolerated (Borison et al., 1982). In an open-label trial with 21 subjects who had an unsatisfactory response to haloperidol, fluphenazine had a superior side effect profile to that of haloperidol in the dose range employed (mean dose of fluphenazine, 7 mg/day, range 2-15 mg/day) (Goetz et al., 1984). In this group selected for an unsatisfactory response to haloperidol, 11 of the 21 subjects (52%) had a better response to fluphenazine than haloperidol, 6 subjects had a comparable response, and 2 subjects preferred haloperidol. 

In open-label trials in children and adults, risperidone was helpful in reducing tics (dose range in children 1-3 mg in two divided doses), with minimal side... 

Pergolide is a mixed D2-D1 agonist used to increase dopaminergic activity in Parkinson s disease. In lower doses, it is believed to have greater effect on presynap-tic D2 autoreceptors than on postsynaptic receptors, which, ultimately, reduces dopaminergic transmission. In a 6-week open-label trial of pergolide in 32 patients (ages 7-19 years) with TS, three-quarters of subjects reported an improvement of at least 50% in tic severity, at a mean dose of 177 61 j,g in three divided doses. 

The opioid antagonist naltrexone was subsequently investigated as a treatment for the associated target symptoms of autistic disorder, in addition to the core social impairment. Results from open-label trials and... 

Olanzapine. To date, case reports and an open-label case series have described positive responses to the atypical antipsychotic olanzapine in subjects with PDDs. In the case series, six of seven children, adolescents, and adults with autistic disorder and other PDDs (mean age, 20.9 +/— 11.7 years range 5-42 years) who completed the 12-week open-label trial were responders (Potenza et al., 1999). Significant improve-... 

To more rigorously address the pharmacotherapy of symptoms of hyperactivity and inattention in PDD, the NIMH-sponsored RUPP Autism Network is conducting a controlled investigation of methylphenidate versus placebo in children and adolescents with PDDs. Nonresponders to methylphenidate will have the opportunity to enter a prospective, open-label trial of guanfacine. 

There have been three randomized clinical trials and multiple case reports and open-label trials with the tricyclic antidepressants (TCAs) in PTSD, although only one study of childhood PTSD (Southwick et al., 1994) has been reported. Robert et al. (1999) reported the use of low-dose imipramine (1 mg/kg) to treat symptoms of ASD in children with burn injuries. In this study, 25 children ages 2 to 19 years were randomized to receive either chloral hydrate or imipramine for 7 days. Ten of 12 subjects receiving imipramine experienced from half to full remission of ASD symptoms, whereas 5 of 13 subjects responded to chloral hydrate. Sleep-related flashbacks and insomnia appeared to be particularly responsive to treatment. 

Trauma exposure may induce sensitization or kindling phenomena in limbic nuclei in the human CNS. A number of successful open-label trials have been conducted with antikindling/anticonvulsive agents with adult PTSD patients. 

Cornelius, J., Bukstein, O., Birmaher, B., Salloum, O., Lynch, K., Pollock, N., Gershon, S., and Clark, D. (2001) Fluoxetine in adolescents with major depression and alcohol use disorder an open-label trial. Addict Behav 26 735—739. 

All of the above trials were conducted in adults and, to the best of our knowledge, there are no trials of antipsychotic medication in children with psychoses and MR. To date there have been two double-blind trials of antipsychotic drugs in normal-IQ children and adolescents with schizophrenia, as well as several open-label trials (Ernst et al., 1999). The majority of these studies and case reports have demonstrated substantial reductions in schizophrenic symptoms. Given the lack of data on children and adolescents having both MR and schizophrenia, it seems that clinicians have little choice but to follow the standard of care applied with normal-IQ schizophrenic children, namely to use anti-... 

Munjack et al. [1991] conducted a pilot study of buspirone in the treatment of social phobia. Subjects meeting DSM-lll-R criteria for social phobia were entered into an 8-week, open-label trial. Buspirone was started at 5 mg twice a day and increased by 5 mg every 2-3 days to a maximum dosage of 60 mg/day, or until side effects prevented further dose escalation. Of the 17 subjects entered in this study, 11 completed it. The 6 dropouts resulted from lack of responsiveness, adverse effects, inability to attend appointments, and a loss to follow-up. At week 6, of the 11 subjects completing the trial, 5 reported a little and 6 endorsed moderate change in their symptomatology. At the end of week 8, two subjects reported a little, 5 noted moderate, and 4 endorsed marked improvement. Although the global measures demonstrated the above results, instruments used to measure the features specific to social phobia demonstrated mixed results. 

Novel and experimental drug treatments. A variety of alternative drug treatments have been used in OCD. Of those considered here, intravenous clomipramine is the only treatment supported by a reasonable degree of empirical evidence. Several open-label trials suggest that intravenous administration of clomipramine may be helpful in patients with OCD that is refractory to oral clomipramine (Fallon et al. 1992 Thakur et al. 1991 Warneke 1989]. 

Kratochvil CJ, Bohac D, Harrington M, et al An open-label trial of atomoxetine in pediatric attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11 167—170, 2001... 

Kratochvil CJ, Heiligenstein JH, Dittmann R, et al Atomoxetine and methylphenidate treatment in children with ADHD a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 41 776-784, 2002... 

METHODOLOGY TO MINIMIZE BIAS IN OPEN-LABEL TRIALS... 

The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a 29-item self-rating scale for the evaluation of depressive symptom severity. Each item is rated on a defined four-step scale (0 3). Analysis of sensitivity to change in symptom severity in an open-label trial showed that the IDS-SR was highly correlated with the 17-item HRSD (Rush et at., 1996). 

As with other drugs, a methodologically rigorous study addressing this issue has not been done with venlafaxine. Nevertheless, there are data from an open-label trial of venlafaxine that warrant comment (149). In this study, high-dose venlafaxine produced an acute response in more than 30% of patients who had historically not adequately benefited from adequate trials of at least three antidepressants from different classes or two antidepressants plus ECT. Until more definitive data are available, this study does support a trial of high-dose venlafaxine in such patients. 

---