Results of a follow-up investigation to a clinical trial testing the efficacy of clomipramine in the treatment of separation anxiety in dogs

The objective of the study was to investigate the incidence of adverse events and changes in behaviour after use of clomipramine to treat separation anxiety in dogs. This study was a follow-up investigation to a previously published clinical trial. In the main trial, dogs were randomised in a double-blinded manner to receive placebo, standard (1–2 mg/kg, q12h) or low (0.5–1 mg/kg, q12h) dosages of clomipramine for 2–3 months. All dogs received behavioural therapy. Follow-up questionnaires were completed in 76 out of 89 dogs between 5.5 and 16 months after completion of the main trial. Post study, 12 dogs at one site received clomipramine long term (>13–16 months). The clomipramine was tolerated well, no dogs had worsening of their behaviour and behaviour improved further in 10 (83%) dogs. An additional 16 dogs received clomipramine and/or other drugs for up to 30 weeks and 48 cases received no drugs post trial. Acute worsening of behaviour was noted in the first two weeks after stopping treatment in three cases receiving low dose clomipramine, but in no cases in the other groups. The worsening rate of separation anxiety >2 weeks after stopping therapy was 13% of dogs that had received standard-dose clomipramine, 15% of dogs that had received low dose clomipramine and 23% of dogs that had received placebo. The mean time to worsening was longer in dogs that had received standard-dose clomipramine (37 weeks), as compared to low dose clomipramine (11 weeks, P = 0.005) or placebo (11 weeks, P = 0.003). In conclusion, no undesirable long term effects were detected in the use of standard-dose (1–2 mg/kg, q12h) clomipramine for the treatment of separation anxiety in dogs. Abrupt withdrawal of a sub-optimal dose of clomipramine (0.5–1 mg/kg, q12h) before signs of anxiety have been well controlled is not recommended.