title: Potential benefits of slow titration of paroxetine treatment in an elderly population: eight-week results from a naturalistic setting.
abstract: BACKGROUND
  Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population.
  
  
  METHODS
  In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline).
  
  
  RESULTS
  Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration).
  
  
  CONCLUSIONS
  Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.
authors.affiliation: Institute of Psychiatry, University of Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gibiino
authors.forename: Elisa
authors.initials: E
authors.lastname: Mori
authors.forename: Diana
authors.initials: D
authors.lastname: De Ronchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016009:Chi-Square Distribution; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D017374:Paroxetine / Q000008:administration & dosage* / Q000009:adverse effects; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine