Amodeo, L., Castelli, L., Leombruni, P., Cipriani, D., Biancofiore, A., & Torta, R. (2011). Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: A pilot study. Supportive Care in Cancer, 20, 375–384.

 To compare the tolerability and efficacy of two different titrations of paroxetine in a population of patients with cancer who have depression

Patients who were randomized to slow up-titration started paroxetine 2.5 mg/day, increasing the daily dose by 2.5 mg each third day, until 10 mg/day was reached on day 8. On day 9, the dosage was increased to 15 mg/day, and on day 11, patients reached the full dose of 20 mg/day.

Patients who were randomized to standard up-titration started with 10 mg/day of paroxetine and increased the daily dose to 20 mg/day on day 8.

• The sample size was 20.
• The median age of the slow up-titration group was 60 (range = 40–78), and the median age of the standard up-titration group was 64 (range = 43–78).
• The sample was 30% male and 70% female.
• Cancer types included breast (30%), lung (20%), colorectal (20%), hematologic (10%), head and neck (6.7%), gastric (3.3%), dermatologic (3%), and others (6.7%).
• 46.7% had no active disease, 30% had local active disease, and 23.3% had metastatic disease. 
• For inclusion, patients had to have any stage of cancer and a major depressive disorder or adjustment disorder with depressed mood. By DMS criteria, 30% had major depression and 50% had adjustment disorder with depressed mood.

• Single site
• Outpatient setting  
• Turin, Italy
   

• Active treatment
• Late effects and survivorship
   

Open randomized trial  

• Dosage Record and Treatment Emergent Symptom Scale
• Subjective Side Effects From Medication Scales
• Hospital Anxiety and Depression Scale
• Montgomery Asberg Depression Rating Scale (MADRS)
• European Organization for Research and Treatment of Cancer–Quality-of-Life Questionnaire Core 30
• Hamilton Rating Scale for Anxiety (Clinical Global Impression and Patient Global Impression of Improvement)
   

Both treatment groups showed a significant mood improvement. A significantly higher rate of patients in the slow up-titration group2, compared to the standard titration group, showed no side effects after two weeks (p = 0.005). A total of 46.7% of subjects used in the intent-to-treat analysis were considered responders, according to MADRS results. Nine patients (30%) dropped out because of side effects that included gastrointestinal problems, dizziness, confusion, restlessness, and tremors. The majority of side effects appeared within the first two weeks.

Slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in patients with cancer who have depression. Fewer than half the patients in the final sample were identified as responders to treatment, and a third discontinued the treatment because of the drug's side effects.

• The sample was small, containing fewer than 30 participants.
• No control group was used. 
• The drop-out rate was high. 
• At baseline patients' severity of depressive symptoms at baseline varied.

Slow up-titration is better tolerated and may support patient compliance.

A large proportion of patients had side effects that caused them to discontinue treatment. In the general population, side effects from antidepressants are associated with discontinuation of treatment. In patients with cancer who may already have significant symptom burden, the benefits of antidepressant treatment need to be considered in this context.

Among patients with cancer, it is not yet clear which patients actually benefit from medication to counter depressive symptoms.