Changes

*Impaired liver function (TCAs metabolised by liver)

*Impaired liver function (TCAs metabolised by liver)

*Hyperthyroidism (enhanced response to TCAs)

*Hyperthyroidism (enhanced response to TCAs)

*Urinary retention <ref>Overall, K.L. 2001. Pharmacological Treatment in Behavioural Medicine: The Importance of Neurochemistry, Molecular Biology and Mechanistic Hypotheses. The Veterinary Journal, 162, 9-23</ref>.

*Urinary retention <ref name="Overall5">Overall, K.L. (2001). Pharmacological Treatment in Behavioural Medicine: The Importance of Neurochemistry, Molecular Biology and Mechanistic Hypotheses. The Veterinary Journal, 162, 9-23</ref>.

===Interactions===

===Interactions===

==Clomipramine==

==Clomipramine==

*Licensed preparation: Clomicalm (dog).

*Licensed preparation: Clomicalm (dog).

:*License indication: Separation anxiety<ref>Clomipramine hydrochloride [http://www.clomicalm.novartis.us/pdf/Clomicalm-product-info.pdf data sheet]</ref>

:*License indication: Separation anxiety<ref>Clomipramine hydrochloride [http://www.clomicalm.novartis.us/pdf/Clomicalm-product-info.pdf data sheet] (accessed April 2015)</ref>

*Unlicensed/off-label uses

*Unlicensed/off-label uses

:*Anxiety related problems, especially those involving panic.

:*Anxiety related problems, especially those involving panic.

:*[[Indoor Marking - Cat|Feline indoor spray marking]] where anxiety, especially chronic, is a factor (if problem is longstanding or refractory to behavioural treatment).

:*[[Indoor Marking - Cat|Feline indoor spray marking]] where anxiety, especially chronic, is a factor (if problem is longstanding or refractory to behavioural treatment).

For dose, consult appropriate data sheets and references. Onset of action is 4 or more weeks. The dose of clomipramine may need to be increased if the response is insufficient after 6-8 weeks. Higher doses are associated with increased adverse effects such as sedation and it is important that genuine response to therapy is not confused with undesirable profound sedative effects which will suppress all sorts of behaviour. Sensitivity of cats to TCAs is generally higher than in dogs as they use glucuronidation to metabolise them<ref>Overall, K.L., 2004. Paradigms for pharmacologic use as a treatment component in feline behavioral medicine. Journal of Feline Medicine and Surgery 6, 29-42.</ref>.  

For dose, consult appropriate data sheets and references. Onset of action is 4 or more weeks. The dose of clomipramine may need to be increased if the response is insufficient after 6-8 weeks. Higher doses are associated with increased adverse effects such as sedation and it is important that genuine response to therapy is not confused with undesirable profound sedative effects which will suppress all sorts of behaviour. Sensitivity of cats to TCAs is generally higher than in dogs as they use glucuronidation to metabolise them<ref name ="Overall1" />.  

Once the condition being treated is deemed under control, drug therapy can be gradually phased out over a period of 1 week per month of treatment. Sudden withdrawal of medication can lead to relapse, withdrawal effects or discontinuation syndrome, especially with short half-life SRI/SSRI drugs. Successful drug therapy should produce around 70% reduction in the behaviour and an increase in normal activity as a substitute.

Once the condition being treated is deemed under control, drug therapy can be gradually phased out over a period of 1 week per month of treatment. Sudden withdrawal of medication can lead to relapse, withdrawal effects or discontinuation syndrome, especially with short half-life SRI/SSRI drugs. Successful drug therapy should produce around 70% reduction in the behaviour and an increase in normal activity as a substitute.

*Licensed preparation: Reconcile (dog). Currently unavailable in Europe.

*Licensed preparation: Reconcile (dog). Currently unavailable in Europe.

:*License indication: Treatment of canine separation anxiety in conjunction with behaviour modification in dogs over 6 months old<ref>Landsberg, G.M., Melese, P., Sherman, B.L., Neilson, J.C., Zimmerman, A., Clarke, T.P., 2008. Effectiveness of fluoxetine chewable tablets in the treatment of canine separation anxiety. Journal of Veterinary Behavior 3, 12-19</ref><ref>Dodman, N.H., Shuster, L., 1994. Pharmacologic approaches to managing behaviour problems in small animals. Vet. Med. 89, 960-969.</ref><ref>Beaver, B.V., 1999. Canine Behavior: A Guide for Veterinarians. W.B. Saunders Company, Philadelphia, PA, pp. 26-28.</ref><ref>Overall, K.L., 2001. Pharmacological treatment in behavioral medicine: the importance of neurochemistry, molecular biology and mechanistic hypotheses. Vet. J. 162, 9-23.</ref><ref>Landsberg, G., Hunthausen, W., Ackerman, L., 2003. In: Handbook of Behavior Problems of the Dog and Cat, 2nd ed. Elsevier Saunders, Philadelphia, pp. 258-267.</ref><ref>Simpson, B.S., Papich, M.G., 2003. Pharmacologic management in veterinary behavioral medicine. Vet. Clin. North Am.: Small Anim. Pract. 33, 365-404.</ref><ref name="Simpson">Simpson, B.S., Landsberg, G.M., Reisner, I.R., Ciribassi, J.J., Horwitz, D., Houpt, K.A., Kroll, T.L., Luescher, A., Moffat, K.S., Douglass, G., Robertson-Plouch, C., Veenhuizen, M.F., Zimmerman, A., Clark, T.P., 2007. Effects of Reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety. Vet. Ther. 8, 18-31. Sonawalla, S.</ref>.

:*License indication: Treatment of canine separation anxiety in conjunction with behaviour modification in dogs over 6 months old<ref>Landsberg, G.M., Melese, P., Sherman, B.L., Neilson, J.C., Zimmerman, A., Clarke, T.P., 2008. Effectiveness of fluoxetine chewable tablets in the treatment of canine separation anxiety. Journal of Veterinary Behavior 3, 12-19</ref><ref>Dodman, N.H., Shuster, L., 1994. Pharmacologic approaches to managing behaviour problems in small animals. Vet. Med. 89, 960-969.</ref><ref>Beaver, B.V., 1999. Canine Behavior: A Guide for Veterinarians. W.B. Saunders Company, Philadelphia, PA, pp. 26-28.</ref><ref name="Overall5" /><ref>Landsberg, G., Hunthausen, W., Ackerman, L., 2003. In: Handbook of Behavior Problems of the Dog and Cat, 2nd ed. Elsevier Saunders, Philadelphia, pp. 258-267.</ref><ref>Simpson, B.S., Papich, M.G., 2003. Pharmacologic management in veterinary behavioral medicine. Vet. Clin. North Am.: Small Anim. Pract. 33, 365-404.</ref><ref name="Simpson">Simpson, B.S., Landsberg, G.M., Reisner, I.R., Ciribassi, J.J., Horwitz, D., Houpt, K.A., Kroll, T.L., Luescher, A., Moffat, K.S., Douglass, G., Robertson-Plouch, C., Veenhuizen, M.F., Zimmerman, A., Clark, T.P., 2007. Effects of Reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety. Vet. Ther. 8, 18-31. Sonawalla, S.</ref>.

*Unlicensed/off-label uses

*Unlicensed/off-label uses

:*Compulsive disorders<ref>Altemus, M., Glowa, J. R. & Murphy, D. L., 1993. Attenuation of food restriction-induced running by chronic fluoxetine treatment. Psychopharmacology Bulletin 29, 397–400.</ref>

:*Compulsive disorders<ref>Altemus, M., Glowa, J. R. & Murphy, D. L., 1993. Attenuation of food restriction-induced running by chronic fluoxetine treatment. Psychopharmacology Bulletin 29, 397–400.</ref>

:*Feline Urine Marking

:*Feline Urine Marking

As with other drugs used to treat behavioural problems it is recommended that fluoxetine be used in conjunction with behavioural modification techniques <ref name="Simpson" /><ref>Petit, S., Pageat, P., Chaurand, J.P., Heude, B., Beata, C., 1999. Efficacy of clomipramine in the treatment of separation anxiety in dogs: clinical trial. Rev. Med. Vet. 2, 133-140.</ref><ref>King, J.N., Simpson, B.S., Overall, K.L., Appleby, D., Pageat, P., Ross, C., Chaurand, J.P., Heath, S., Beata, C., Weiss, A.B., Muller, G., Paris, T., Bataille, B.G., Parker, J., Petit, S., Wren, J., 2000. Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo controlled, parallel-group, multicenter clinical trial. Appl. Anim. Behav. Sci. 67, 255-275.</ref><ref>Seksel, K., Lindeman, M.J., 2001. Use of clomipramine in treatment of obsessive-compulsive disorder, separation anxiety and noise phobia in dogs: a preliminary, clinical study. Aust. Vet. J. 79, 252-256.</ref><ref>Horwitz, D., 2000. Diagnosis and treatment of canine separation anxiety and the use of clomipramine hydrochloride. J. Am. Anim. Hosp. Assoc. 36, 107-109.</ref><ref>Takeuchi, Y., Houpt, K.A., Scarlett, J.N., 2000. Evaluation of treatments for separation anxiety in dogs. J. Am. Vet. Med. Assoc. 217, 342-345.</ref><ref>Landsberg, G., Hunthausen, W., Ackerman, L., 2003. In: Handbook of Behavior Problems of the Dog and Cat, 2nd ed. Elsevier Saunders, Philadelphia, pp. 258-267.</ref>. Although effects are allay seen within 4-6 weeks, 6-8 weeks should be allowed before making an assessment of efficaciousness. The long half-life of fluoxetine and its metabolites also mean that a period of at least 6 weeks should be allowed to pass before administration of any drugs which may interact adversely.

As with other drugs used to treat behavioural problems it is recommended that fluoxetine be used in conjunction with behavioural modification techniques <ref name="Simpson" /><ref>Petit, S., Pageat, P., Chaurand, J.P., Heude, B., Beata, C., 1999. Efficacy of clomipramine in the treatment of separation anxiety in dogs: clinical trial. Rev. Med. Vet. 2, 133-140.</ref><ref>King, J.N., Simpson, B.S., Overall, K.L., Appleby, D., Pageat, P., Ross, C., Chaurand, J.P., Heath, S., Beata, C., Weiss, A.B., Muller, G., Paris, T., Bataille, B.G., Parker, J., Petit, S., Wren, J., 2000. Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo controlled, parallel-group, multicenter clinical trial. Appl. Anim. Behav. Sci. 67, 255-275.</ref><ref>Seksel, K., Lindeman, M.J., 2001. Use of clomipramine in treatment of obsessive-compulsive disorder, separation anxiety and noise phobia in dogs: a preliminary, clinical study. Aust. Vet. J. 79, 252-256.</ref><ref>Horwitz, D., 2000. Diagnosis and treatment of canine separation anxiety and the use of clomipramine hydrochloride. J. Am. Anim. Hosp. Assoc. 36, 107-109.</ref><ref>Takeuchi, Y., Houpt, K.A., Scarlett, J.N., 2000. Evaluation of treatments for separation anxiety in dogs. J. Am. Vet. Med. Assoc. 217, 342-345.</ref><ref>Landsberg, G., Hunthausen, W., Ackerman, L., 2003. In: Handbook of Behavior Problems of the Dog and Cat, 2nd ed. Elsevier Saunders, Philadelphia, pp. 258-267.</ref>. Although effects are generally seen within 4-6 weeks, 6-8 weeks should be allowed before making an assessment of efficaciousness. The long half-life of fluoxetine and its metabolites also mean that a period of at least 6 weeks should be allowed to pass before administration of any drugs which may interact adversely.

==References==

==References==

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{{Jon Bowen reviewed

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[[Category:Pharmacological Approach to Problem Behaviour]]

[[Category:Pharmacological Approach to Problem Behaviour]]