PMID- 18840371
OWN - NLM
STAT- MEDLINE
DCOM- 20090106
LR  - 20151119
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 30
IP  - 9
DP  - 2008 Sep
TI  - Short-term tolerability of a nonazapirone selective serotonin 1A agonist in 
      adults with generalized anxiety disorder: a 28-day, open-label study.
PG  - 1658-66
LID - 10.1016/j.clinthera.2008.09.006 [doi]
AB  - BACKGROUND: The serotonin 1A (5-hydroxytryptamine 1A [5-HT1A]) receptor likely 
      plays a critical role in anxiety pathophysiology. OBJECTIVE: In this 
      proof-of-concept investigation, we tested the short-term tolerability of 
      PRX-00023, a nonazapirone 5-HT1A selective partial agonist, in outpatients with 
      generalized anxiety disorder (GAD). METHODS: Patients with a diagnosis of GAD, as 
      defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth 
      Edition, and Hamilton Anxiety (HAM-A) Rating Scale scores > or =20 were 
      recruited. A 1-week, single-blind placebo run-in was followed by a 
      28-day,open-label treatment with PRX-00023 QD in a forced-titration protocol: 40 
      mg (days 1-4), 80 mg (days 5-14), and 120 mg (days 15-28). The primary outcome 
      measures were tolerability and rate of completion of the study. Tolerability was 
      recorded using a table of adverse events (AEs), and measured using laboratory 
      tests, vital signs, and electrocardiogram (ECG) readings. Secondary outcomes 
      included the baseline-to-end point change in HAM-A total score, percentage 
      meeting remission (HAM-A< or =7), and response criteria (> or =50% reduction in 
      HAM-A total score). RESULTS: Twenty-three patients (56.5% female, 65.2% white; 
      mean age, 37.4 years) were enrolled in the study. A total of 21 patients (91.3%) 
      received study medication and 18 (78.3%) completed the study. Two patients 
      withdrew for personal reasons, 1 was discontinued for noncompliance, and 1 was 
      lost to follow-up. One patient was discontinued from the study due to a history 
      of premature ventricular contractions deemed unrelated to the study drug. AEs 
      were reported in 15 patients, with the most common being back pain (3 patients), 
      influenza-like symptoms (without fever) (2), diarrhea (2), dyspepsia (2), and 
      nausea (2). No serious AEs, withdrawal symptoms, ataxia/ dizziness, or sexual 
      dysfunction were reported; there were no clinically significant laboratory, vital 
      sign, or ECG abnormalities. Mean HAM-A total scores were significantly lower at 
      study end point compared with enrollment (13.9 vs 22.9; P < 0.001), with 32% of 
      patients achieving remission and 52% meeting response criteria. CONCLUSION: In 
      this preliminary, short-term study, PRX-00023 appeared to be generally well 
      tolerated in this sample of patients with GAD.
FAU - Mathew, Sanjay J
AU  - Mathew SJ
AD  - Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 
      10029, USA. sanjay.mathew@mssm.edu
FAU - Garakani, Amir
AU  - Garakani A
FAU - Reinhard, John F Jr
AU  - Reinhard JF Jr
FAU - Oshana, Scott
AU  - Oshana S
FAU - Donahue, Stephen
AU  - Donahue S
LA  - eng
GR  - K23MH069656/MH/NIMH NIH HHS/United States
GR  - M01-RR-00071/RR/NCRR NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin 5-HT1 Receptor Agonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Sulfonamides)
RN  - LQ54E5B4EW (naluzotan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Anxiety Agents/administration & dosage/*therapeutic use
MH  - Anxiety Disorders/diagnosis/*drug therapy/psychology
MH  - Diagnostic and Statistical Manual of Mental Disorders
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperazines/administration & dosage/adverse effects/*therapeutic use
MH  - Psychiatric Status Rating Scales
MH  - Serotonin 5-HT1 Receptor Agonists
MH  - Serotonin Receptor Agonists/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Single-Blind Method
MH  - Sulfonamides/administration & dosage/adverse effects/*therapeutic use
MH  - Surveys and Questionnaires
MH  - Treatment Outcome
EDAT- 2008/10/09 09:00
MHDA- 2009/01/07 09:00
CRDT- 2008/10/09 09:00
PHST- 2008/07/02 00:00 [accepted]
PHST- 2008/10/09 09:00 [pubmed]
PHST- 2009/01/07 09:00 [medline]
PHST- 2008/10/09 09:00 [entrez]
AID - S0149-2918(08)00299-3 [pii]
AID - 10.1016/j.clinthera.2008.09.006 [doi]
PST - ppublish
SO  - Clin Ther. 2008 Sep;30(9):1658-66. doi: 10.1016/j.clinthera.2008.09.006.