Antidepressants open-label study

Atypical Antidepressants. Preliminary open label studies suggested that ven-lafaxine and trazodone might be effective for OCD. However, controlled studies have not yet been completed for venlafaxine, and a controlled study of trazodone (100-200 mg/day) did not find it an effective treatment for OCD. 

Atypical Antidepressants. Initial open label studies of nefazodone and mir-tazapine have been conducted and offer promise, though one negative controlled study with the former has been reported. Further studies are needed. 

With regard to the specific action of antidepressants on the dopaminergic system, there is evidence that buproprion (not marketed in most countries in Western Europe as an antidepressant but available in North America), amineptine and nomifensin (withdrawn because of the rare occurrence of haemolysis) owed their antidepressant efficacy to their ability to increase central dopaminergic function. There are also open label studies to suggest... 

Venlafaxine. Venlafaxine (Effexor) possesses both SSRI and TCA properties (noradrenergic and serotonergic) and is chemically unrelated to other antidepressants. Several open-label studies of adults with ADHD (N = 61) (Adler, et al. 1995 Hornig-Rohan and Amsterdam, 1995 Reimherr et al., 1995 Findling et al., 1996) and one such study of children (Luh et al., 1996) have all shown promising results and support further investigation through controlled trials. 

Other new antidepressants, including bupropion, ven-lafaxine, nefazodone, and mirtazapine, have been found to be efficacious in the treatment of depressed adults, but only a few open-label studies have been carried out in children and adolescents (e.g., Daviss et ah, 2001). Bupropion and velanfaxine may be useful in treating youth with MDD and ADHD (Plizka, 2000 Daviss et ah, 2001). Because of the sedative effects of mirtazapine and trazodone, these medications have been used as adjunctive treatments for patients with severe insomnia. 

Mirtazapine is an antidepressant with a novel mechanism of action affecting both 5-HT and noradrenergic function. A recent systematic, open-label study found that 9 (34.6%) of 26 subjects (5 females, 21 males mean age, 10.1 +/— 4.8 years, age range 3.8-23.5 years) with autistic disorder and other PDDs were much improved or very much improved on the CGI after a mean duration of treatment of 5 months (Posey et al., 2001). The dosage range for mirtazapine was 7.5 to 45 mg/day with a mean daily dose of 30.29 mg +/— 12.64 mg. Target symptoms of aggression, self-injury, irritability, hyperactivity, anxiety, depression, and insomnia showed improvement. Adverse effects were transient and minimal and included increased appetite, irritability, and sedation. Based upon these preliminary data, a double-blind, placebo-controlled trial appears warranted. 

In the Zito et al. study (2000), antidepressants were the second most commonly prescribed psychotropic medication. There are a total of 10 studies or case reports in the literature examining antidepressant use in preschool children (Table 49.4). None of the 10 studies are randomized, double-blind, or placebo-controlled trials. The ten uncontrolled studies looked at a total of 37 preschool children. Six of the studies looked at a total of 29 preschoolers with autism or childhood schizophrenia (Campbell et ah, 1971a Petti and Campbell, 1975 Holttum et ah, 1994 Sanchez et ah, 1996 DeLong et ah, 1998 Hollander et ah, 2000). While these six studies are difficult to compare, given the small sample sizes and the different treatment medications, these open-label studies suggest that clomipramine, venlafaxine, and fluoxetine may be helpful to reduce some psychiatric symptoms found in autistic... 

As a results of these studies, clinicians have proposed that switching to reboxetine or bupropion might a useful strategy given that these antidepressants share the ability with desipramine and imipramine to block NE uptake. Nevertheless, only one small open label study has been done to test this possibility ( 365). If bupropion is to be used in patients switched from an ineffective trial of fluoxetine, the dose should be kept low for several weeks to allow for the clearance of fluoxetine and norfluoxetine. Case reports indicate that fluoxetine can elevate levels of the active metabolites of bupropion, which, in turn, could mediate an increase risk of adverse effects (366). 

Results of low-dose risperidone (0.5 to 2 mg/day) added to antidepressant therapy in refractory patients are encouraging. Treatment response over 6 weeks was rapid and consistent. An additional 8-week, open-label study reported that 50% of patients previously unresponsive to clomipramine responded after risperidone 3 mg/day was added. The recommended initial dose of risperidone is 0.25 mg, and the target dose is 0.5 to 5 mg/day. Thirty-six patients unresponsive to antidepressants were given risperidone, up to 6 mg/day or placebo in a double-blind trial. Risperidone treatment resulted in a significant reduction in YBOCS scores. " In an open-label trial of olanzapine augmentation of SSRIs for 8 weeks, most patients experienced complete or partial remission in doses of 1.25 to 20 mg/day. ... 

For perimenopausal depression, antidepressants usually are dosed daily at standard dosages for major depression, although some women may respond to lower doses. Estradiol deficiency may decrease the activity of 5-HT and decrease the efficacy of antidepressants. Two open-label studies have reported that citalopram in doses of 20-60 mg/day was effective in treating depression in peri- and postmenopausal women and had augmenting effects in depressed subjects who were still symptomatic after treatment with transdermal estradiol (i.e., improved symptoms of anxiety and somatic complaints). " ... 

Schille C, Baghai TC, Eser D, Nothdurfter C, Rupprecht R. Lithium but not carbamazepine augments antidepressant efficacy of mirtazapine in unipolar depression an open-label study. World J Biol Psychiatry 2009 10 390-9. 

Vilazodone is both an SSRI and a partial serotonin 5-HTl A receptor agonist. In January 2011, vilazodone received FDA approval as an antidepressant suitable for use in adults. To date there have been relatively few reports concerning the adverse effect profile of vilazodone the available data mainly derive from two Phase 111 trials and an open label study. In a 1-year open-label study assessing the safety and tolerability of vilazodone in subjects with major depressive disorder, the most common adverse effects were diarrhoea (37.5%), nausea (31.6%) and headache (20.0%) however more than 90% of these adverse effects were rated as only mild or moderate http //en.wikipedia.org/wi ki/Vilazodonehttp //en.wikipedia.org/wiki/Vilazodone - cite note-intj-6 [90 -]. These adverse effects were somewhat higher than from the pooled Phase HI data, where the rates of these side effects were diarrhoea (28.4%), nausea (23.4%) and headache (13.3%) [91E,92E]. 

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. 

Lambert 1984 McElroy et al. 1988b] suggested that valproate may be a much better antimanic than antidepressant agent. In a study of 78 consecutively recruited patients with rapid-cycling bipolar disorder treated with open-label valproate alone or in combination with other psychotropic agents, Calabrese and colleagues [Calabrese and Delucchi 1990 Calabrese et al. 1992] reported a 54% valproate response in acute mania, an 87% response in acute mixed states, and a 19% response in acute depression. However, they did observe a prophylactic antidepressant effect in patients subsequently. Additional controlled studies are needed to clarify valproate s antidepressant efficacy. 

Several trials have been performed with antidepressants in the prevention of recurrence of major depression. In an exemplary trial of this kind, Reimherr et al. (1998) explored the optimal length of therapy in a long-term, placebo-controlled continuation study of patients who had responded to 12 14 weeks of open-label fluoxetine treatment (20mg/day) for major depression. Different maintenance schedules were represented by four treatment arms ... 

Few data are available to guide this decision beyond clinical experience. There is a modest amount of evidence that nonresponders to TCAs, principally desipramine or imipramine, alone may respond to a SSRI alone and vice versa (136). No compelling evidence exists showing that nonresponders to one SSRI as a result of a lack of efficacy will respond to a second trial with another SSRI. There is limited confidence in the results of studies that have been done switching nonresponders from one SSRI to another for two reasons. First, virtually all have been open label and, second, most were conducted by the manufacturer of the second SSRI. Until there is more substantive evidence that switching from one SSRI to another is worthwhile, it may be more prudent to switch to a class of antidepressants with a different putative mechanism of action. 

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. 

Risperidone Acute Clinical Trials. Hillert et al. (107) found risperidone to have both antipsychotic and antidepressive properties in 10 patients with schizoaffective disorder, depressed type. These investigators prescribed 2 to 10 mg/day for 6 weeks in an open-label pilot study, and found marked improvement in psychosis in all patients and clinically significant overall improvement in psychosis in 7 to 10 patients. Two patients required antiparkinsonian drugs otherwise risperidone was well tolerated by the group. 

Toxicity elevation of serum creatine kinase (CK-MM). In clinical studies (mostly open label), 40% of patients had serum creatine kinase (CK) levels above the upper limit of normal (ULN), and 11% had CK levels that were three times the ULN or more. In cases where CK was fractionated, only the muscle isoenzyme (MM) was elevated. The time to occurrence was sporadic, but the greatest incidence of CK elevation was during the first 2 months of treatment. Elevated CKs were more often seen in males, in patients who were being treated with antidepressants or anti-epileptics, and in patients treated with intrathecal morphine. Most patients who experienced elevations in CK, even for prolonged periods of time, did not have limiting side effects. However, one case of symptomatic myopathy with EMG findings and two cases of acute renal failure associated with rhabdomyolysis and extreme CK elevations (17 000-27 000 lU/L) have been reported. It is recommended that physicians monitor serum CK in patients undergoing treatment with ziconotide periodically. 

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