Long-Acting Injectable Antipsychotics in Schizophrenia: Literature Review and Practical Perspective, with a Focus on Aripiprazole Once-Monthly.

INTRODUCTION: Prevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care. METHODS: We narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second-generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors. RESULTS: LAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a "naturalistic" study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years. CONCLUSION: Results across the "full spectrum" of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.

The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients.

The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0 years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score <8) after study treatment had significantly greater early improvement in Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with active study treatment but not with placebo.

[Residential facilities and day centres in mental health. Is there any difference?]. / Strutture residenziali e semiresidenziali nei servizi di salute mentale. Dove sta la differenza?

AIMS: We wanted to investigate to what extent and in what characteristics the patients cared in the psychiatric residential facilities (RF) were similar to those in the day-centres (DC), and whether 6-month improvements in the two settings were comparable. METHODS: We described 141 patients admitted to the RF and 180 in DC of three mental health service networks in Milan and near Milan. They were evaluated again after six months. RESULTS: In both groups, we identified subgroups of more intensive treatment: 45% of those in residential treatment were in high intensity rehabilitation facilities, and those who followed a residential program of >12 hours/week were 53%. The mean duration of treatment in the residential treatment was 40 months (SD 55.7) and in DC 49.6 months (49.3). The two groups differed in the overall scores of the HoNOS, but differences emerged in the subscales relative to daily life activities and living conditions. Among those in RF, about half had a house, versus 99% among those in DC. After six months, clinically significant modifications were small in both groups. CONCLUSIONS: Residential patients had more needs than DC patients. It is possible that some of the residential patients might be treated with intensive DC program, but the absence of a home for the majority of residential facilities patients makes this unlikely.

A survey of five antidepressant properties influencing clinician's treatment choices in MDD.

INTRODUCTION: The goal of the present work was to examine how clinicians' perceptions of the properties of antidepressants may influence their choice of antidepressants when treating major depressive disorder (MDD). METHODS: 273 of 682 (40%) clinicians attending a psychopharmacology review course responded to a questionnaire designed to explore their practices and perceptions with regards to antidepressant pharmacotherapy. RESULTS: Most clinicians ranked efficacy (57.3%) as the most important factor when selecting antidepressants, followed by safety (23.0%), tolerability (9.4%), rapidity of action (5.2%), and cost (4.9%). However, when presented with hypothetical scenarios in which there was a difference in efficacy between two antidepressant agents, the relative safety, tolerability, and cost of the two agents significantly influenced the likelihood of choosing one antidepressant over another. In fact, clinicians required progressively greater differences in efficacy between two agents in order to select one antidepressant over another given a difference in terms of their safety than tolerability, or their tolerability than cost (p < 0.0001 all comparisons). CONCLUSIONS: When selecting an antidepressant, clinicians appear to be most influenced by efficacy, followed by safety. Rapidity of action and cost may be less salient considerations in clinical practice. Further research is necessary to elucidate factors that influence clinicians' choice of antidepressants.

Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine.

BACKGROUND: We assessed the impact of menopausal status on treatment response and well-being in a cohort of outpatient women with major depressive disorder (DSM-III-R criteria), who received treatment with fluoxetine (20 mg/day for 8 weeks). METHODS: Menopausal status was defined based on age, presence of menstrual irregularity or amenorrhea and vasomotor symptoms. Remission and response of depression were defined as a 17-item Hamilton Depression Rating Scale (HAM-D-17) score or=50%, respectively. Well-being was assessed by self-rating with the Symptom Questionnaire. Remitters were followed up for 28 additional weeks. RESULTS: No differences in rates of response and remission as well as in levels of well-being were observed among pre- (n = 121), peri- (n = 28) and postmenopausal (n = 35) women at the endpoint of the acute phase, even after adjustment for baseline depression severity. Residual symptoms, however, were significantly more common in postmenopausal women, except for the continuation phase endpoint. Differences in residual symptoms during the acute phase subsided after adjustment for baseline depression severity. CONCLUSIONS: Overall, menopausal status did not significantly affect the response to fluoxetine treatment and the degree of posttreatment well-being among major depressive disorder patients.