Selective serotonin reuptake inhibitors (SSRIs) are almost unanimously considered to be very efficacious and the first line of pharmacologic treatment for premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). There is a need to examine if this is actually the case. More recently, combined oral contraceptives (COCs) have been pursued due to their ovulation suppression effects. Their effects on PMS/PMDD should be further examined as well.

For this review of the literature from 1990 to the present, MEDLINE, PsychLit, and Cochrane controlled trials register were searched. Randomized, double-blind, placebo-controlled clinical trials of SSRIs and COCs (N>20) that report the rate of responders and not just percent improvement in severity of symptoms were selected for study. The data extraction were the percentage or number of responders as reported by the original authors.

In many studies, only mean improvement in severity was reported. In all studies, the main inclusion criterion was meeting criteria for PMDD; this has not, however, been an outcome measure. However, only 16 reports that provided actual rate of responders could be included. The percentage of non-responders (100% minus active medication) to SSRIs and COCs was found to be higher than the reported percentage of women who responded to active medication (response rate to an SSRI or COC minus the response rate to placebo).

In the majority of larger-scale studies, once the placebo effect is accounted for, the percentage of women who respond to SSRIs or COCs is actually less than the percentage of women who do not respond at all. SSRIs provide an important step forward in the treatment of PMDD and PMS. COCs provide a different option, still, ~40% of women with PMDD do not respond to SSRIs. Treatment with a currently approved COC does not substantially improve the percentage of responders. Therefore, additional alternative targeted treatment modalities need to be developed.

Succinic semialdehyde dehydrogenase (SSADH) deficiency (γ-hydroxybutyric aciduria) is a rare neurometabolic disorder of γ-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology.

We overview the phenotype of 33 adolescents and adults (10.1–39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data.

Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6–12 months of age, 5% from 1–2 years of age, and 14% from 2–4 years of age, mean age at first symptoms was 11±12 months. However, mean age at diagnosis was 6.6±6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had ≥3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized.

The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.

Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6–12 years of age and in adults. In shortterm studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD.

This open-label, multicenter, singlearm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness.

Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P<.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on Clinical Global Impression-Improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated “improved.”

Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.