Changes

==Mechanism of Action==

==Mechanism of Action==

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) which functions by inhibiting the reuptake of serotonin in the pre-synaptic neuron.  

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) which functions by inhibiting the reuptake of serotonin in the pre-synaptic neuron. This inhibition of uptake of reuptake of 5-HT_1A into pre-synaptic neurons is highly selective and does not affect noradrenaline, dopamine, acetylcholine, histaminic or alpha-1 adrenergic receptors. 5-HT_1A receptors have an effect on mood and behaviour. SSRIs are derived from TCAs, such as [[Clomipramine]]. SSRIs act to bring about changes in conformation of receptors, this can take 3-5 weeks<ref>Overall, K.L., 2004. Paradigms for pharmacologic use as a treatment component in feline behavioural medicine. Journal of Feline Medicine and Surgery 6, 29–42</ref>. Regulation of second messengers (cAMP, Ca²⁺, cGMP, IP₃) is responsible for the major effect. Their actions on protein kinases then act to change neuronal metabolism and receptor protein transcription<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>.

Fluoxetine is largely metabolised in the liver by the cytochrome P450 enzyme system to norfluoxetine, also an SSRI.

Fluoxetine is largely metabolised in the liver by the cytochrome P450 enzyme system to norfluoxetine, also an SSRI.

:*Treatment of canine separation anxiety<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> in conjunction with behaviour modification in dogs over 6 months old.

:*Treatment of canine separation anxiety<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> in conjunction with behaviour modification in dogs over 6 months old.

*Unlicensed

*Unlicensed

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>. Fluoxetine has a long half-life and therefore a minimum of 6-8 weeks should be allowed before making an assessment of efficaciousness.

 

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>

Due to the long half-life of fluoxetine it is not necessary to gradually reduce or taper the dose. Once treatment with fluoxetine has ceased continued behavioural modification is advisable to avoid the reappearance of clinical signs. 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.

Due to the long half-life of fluoxetine it is not necessary to gradually reduce or taper the dose. Once treatment with fluoxetine has ceased continued behavioural modification is advisable to avoid the reappearance of clinical signs. 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.

==Adverse Effects==

==Adverse Effects<ref>Fluoxetine hydrochloride [https://www.elancocentral.com/Reconcile_Vet_label.pdf data sheet] ==

*Decreased appetite

*Decreased appetite

*Depression/lethargy

*Depression/lethargy

'''Care should be taken if used in conjunction with any of the following drugs, which may interact and cause adverse effects:'''

'''Care should be taken if used in conjunction with any of the following drugs, which may interact and cause adverse effects:'''

*Fluoxetine should not be given at the same time as drugs which lower seizure threshold eg. phenothiazines such as acepromazine or chlorpromazine.

*Fluoxetine should not be given at the same time as drugs which lower seizure threshold eg. phenothiazines such as acepromazine or chlorpromazine.

*Monoamine oxidase inhibitors (MAOI), or within a period of 2 weeks after discontinuation of treatment with a MAOI.

*Monoamine oxidase inhibitors (MAOI), or within a period of 2 weeks after discontinuation of treatment with a MAOI due to the risk of serotonin syndrome<ref>Brown, T.M., Skop, B.P., Mareth, T.R., 1996. Pathophysiology and management of the serotonin syndrome. The Annals of Pharmacotherapy 30, 527–533.</ref>

*Fluoxetine has not been evaluated with drugs that affect the cytochrome P450 enzyme, care should therefore be taken with any drug that affects the enzyme system eg. ketoconazole.

*Fluoxetine has not been evaluated with drugs that affect the cytochrome P450 enzyme, care should therefore be taken with any drug that affects the enzyme system eg. ketoconazole.