Changes

==Mechanism of Action==

==Mechanism of Action==

Tricyclic group of antidepressants (TCA) are chemically similar to phenothiazines. Amitriptyline and clomipramine are examples of drugs of this type, with clomipramine also being classed as a serotonin re-uptake inhibitor due to its modest serotonergic selectivity.  

The tricyclic group of antidepressants (TCA) are chemically similar to phenothiazines. Amitriptyline and clomipramine are examples of drugs of this type, with clomipramine also being classed as a serotonin re-uptake inhibitor (SRI) due to its modest serotonergic selectivity.  

TCAs have three major effects which vary in degree depending on the specific drug used. These are:  

TCAs have three major effects which vary in degree depending on the specific drug used. These are:  

Together the LC and Raphe nuclei form parts of the ascending reticular activating system that has projections throughout the CNS and is involved in mood, wakefulness, sleep cycles and arousal as well as pain modulation and a host of other maintenance functions such as meal patterning.

Together the LC and Raphe nuclei form parts of the ascending reticular activating system that has projections throughout the CNS and is involved in mood, wakefulness, sleep cycles and arousal as well as pain modulation and a host of other maintenance functions such as meal patterning.

The effect on neurotransmitter levels is quite rapid, but therapeutic effects take 3 weeks or more to become apparent. This is because although clomipramine and many other serotonergic antidepressants (SRI, selective serotonin reuptake inhibitor (SSRI), TCA, atypical) have immediate effects on synaptic neurotransmission, the lasting changes in emotional response are the result of intracellular changes and in altered receptor expression. This is dependent on secondary messenger systems (cAMP, Ca²⁺, cGMP, IP₃), gene expression and protein synthesis that take time to occur. Receptors for nor-adrenaline and serotonin are linked to metabotropic G-proteins that can induce changes in protein synthesis such as the up- and down-regulation of receptors. There are 14 known classes of 5-HT receptors, of these, in anxiety problems the 5-HT₁ receptor is the most relevant.

The effect on neurotransmitter levels is quite rapid, but therapeutic effects take 3 weeks or more to become apparent. This is because although clomipramine and many other serotonergic antidepressants (SRI, selective serotonin reuptake inhibitor (SSRI), TCA and atypical) have immediate effects on synaptic neurotransmission, the lasting changes in emotional response are the result of intracellular changes and in altered receptor expression. This is dependent on secondary messenger systems (cAMP, Ca²⁺, cGMP, IP₃), gene expression and protein synthesis that take time to occur. Receptors for nor-adrenaline and serotonin are linked to metabotropic G-proteins that can induce changes in protein synthesis such as the up- and down-regulation of receptors. There are 14 known classes of 5-HT receptors, of these, in anxiety problems the 5-HT₁ receptor is the most relevant.

For example, in states of anxiety and depression the following presynaptic changes are thought to occur:

For example, in states of anxiety and depression the following presynaptic changes are thought to occur:

*Increase in serotonin in the synaptic cleft.

*Increase in serotonin in the synaptic cleft.

*Increase in stimulation of postsynaptic 5-HT_1A1A-receptors, leading to an elevation of mood (mechanism unknown)

*Increase in stimulation of postsynaptic 5-HT_1A receptors, leading to an elevation of mood (mechanism unknown).

*Increase in CREB and BDNF, leading to normally CNS adaptation to external events

*Increase in CREB and BDNF, leading to normally CNS adaptation to external events.

The exact reason why CREB, BDNF and other neurotropic factors are central to resolving depression and anxiety is to date unclear but it is thought to relate to adaptability of the CNS to external events.

The exact reason why CREB, BDNF and other neurotropic factors are central to resolving depression and anxiety is to date unclear but it is thought to relate to adaptability of the CNS to external events.

Clomipramine and TCAs are far more safely and commonly used in behavioural pharmacology in comparison to benzodiazepines, phenothiazines, barbiturates and sympathomimetic agents.

Clomipramine and TCAs are far more safely and commonly used in behavioural pharmacology in comparison to benzodiazepines, phenothiazines, barbiturates and sympathomimetic agents.

===Selective serotonin reuptake inhibitors (SSRIs)===

===Selective Serotonin Reuptake Inhibitors (SSRIs)===

SSRIs are a group of drugs that all have a greater effect on serotonin reuptake than noradrenaline reuptake. Unlike TCAs, which are named on the basis of chemical structure, the SSRIs are named according to their primary effect on serotonin reuptake. The ratio of serotonin reuptake selectivity in favour varies from around 15:1 (fluoxetine) to more than 150:1 (sertraline). Along with increasing serotonergic selectivity, SSRI drugs also show fewer effects on other neurotransmitter systems. In particular, they are less anticholinergic than TCAs.

SSRIs are a group of drugs that all have a greater effect on serotonin reuptake than noradrenaline reuptake. Unlike TCAs, which are named on the basis of chemical structure, the SSRIs are named according to their primary effect on serotonin reuptake. The ratio of serotonin reuptake selectivity in favour varies from around 15:1 (fluoxetine) to more than 150:1 (sertraline). Along with increasing serotonergic selectivity, SSRI drugs also show fewer effects on other neurotransmitter systems. In particular, they are less anticholinergic than TCAs.

Numerous models of anxiety have been tested in animals. Many are not apparently reliable detectors of anxiolytic effect, and have not been applied to more modern anxiolytic/antidepressant drugs like SSRIs/SRIs. Those in which there is a response to TCA/SRI and SSRI drugs include:

Numerous models of anxiety have been tested in animals. Many are not apparently reliable detectors of anxiolytic effect, and have not been applied to more modern anxiolytic/antidepressant drugs like SSRIs/SRIs. Those in which there is a response to TCA/SRI and SSRI drugs include:

*Approach-avoidance conflict (Stretched approach posture test).

*Approach-avoidance conflict (stretched approach posture test).

*Separation distress vocalisation (guinea pig isolation calls, rat pup isolation ultrasonic vocalisation).

*Separation distress vocalisation (guinea pig isolation calls, rat pup isolation ultrasonic vocalisation).

*Defensive burying in rodents (only some 5-HT reuptake inhibitors)

*Defensive burying in rodents (only some 5-HT reuptake inhibitors).

Interestingly no effect has been found in those tests (so far performed) that involve conditioned fear potentiated startle responses.

Interestingly no effect has been found in those tests (so far performed) that involve conditioned fear potentiated startle responses.

==Adverse Effects<ref>Wiersma, J., Honig, A. & Peters, F. P. J. (2000). Clomipramine-induced allergic hepatitis: a case report. International Journal of Psychiatry in Clinical Practice 4, 69–71.</ref>==

==Adverse Effects<ref>Wiersma, J., Honig, A. & Peters, F. P. J. (2000). Clomipramine-induced allergic hepatitis: a case report. International Journal of Psychiatry in Clinical Practice 4, 69–71.</ref>==

The main adverse effects of this group of drugs is mediated through their effect on histamine (H1) and muscarinic (M1) acetylcholine receptors, as summarised in the table below.

The main adverse effects of this group of drugs are mediated through their effect on histamine (H1) and muscarinic (M1) acetylcholine receptors, as summarised in the table below.

{| class="wikitable"

{| class="wikitable"

|-

|-

The blocking ratio indicates the relative effect of the agent on reuptake of serotonin vs. noradrenaline. Fluoxetine is 3 times more selective for serotonin than clomipramine. Clomipramine was the first TCA whose ratio favours serotonin reuptake inhibition, and hence its title of non-selective serotonin reuptake inhibitor (SRI). The level of anticholinergic effect is usually also decreased with increasing serotonergic selectivity.

The blocking ratio indicates the relative effect of the agent on reuptake of serotonin vs. noradrenaline. Fluoxetine is 3 times more selective for serotonin than clomipramine. Clomipramine was the first TCA whose ratio favours serotonin reuptake inhibition, hence its title of non-selective serotonin reuptake inhibitor (SRI). The level of anticholinergic effect is usually also decreased with increasing serotonergic selectivity.

'''Caution should be taken if the animal suffers from any of the following pre-existing medical conditions:'''

'''Caution should be taken if the animal suffers from any of the following pre-existing medical conditions:'''

*Heart disease, especially heart block and arrythmias <ref>Pouchelon, J. L., Martel, E., Champeroux, P., Richard, S. & King, J. N. (2000). Effect of clomipramine hydrochloride on the electrocardiogram and heart rate of dogs. American Journal of Veterinary Research, in press.</ref><ref>Reich, M. R., Ohad, D. G., Overall, K. L. & Dunham, A. E. (2000). Electrocardiographic assessment of antianxiety medication in dogs and correlation with drug serum concentration. Journal of the American Veterinary Medical Association 216, 1571–5.</ref>

*Heart disease, especially heart block and arrythmias <ref>Pouchelon, J. L., Martel, E., Champeroux, P., Richard, S. & King, J. N. (2000). Effect of clomipramine hydrochloride on the electrocardiogram and heart rate of dogs. American Journal of Veterinary Research, in press.</ref><ref>Reich, M. R., Ohad, D. G., Overall, K. L. & Dunham, A. E. (2000). Electrocardiographic assessment of antianxiety medication in dogs and correlation with drug serum concentration. Journal of the American Veterinary Medical Association 216, 1571–5.</ref>

*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===

'''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 severe adverse effects:'''

*Opioids (e.g. morphine): enhanced analgesia and respiratory depression.

*'''Opioids''' (e.g. morphine): enhanced analgesia and respiratory depression.

*MAOIs: risk of serotonin syndrome, advise washout period of 2-3 weeks between treatment with these drugs<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>.

*'''MAOIs''': risk of serotonin syndrome, advise washout period of 2-3 weeks between treatment with these drugs<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>.

*Phenothiazines: increased shared adverse effects (CVS, etc), mutual increase in serum levels due to competition for cytochrome p450. Definite risk of severe adverse affects and toxicity.

*'''Phenothiazines''': increased shared adverse effects (CVS, etc), mutual increase in serum levels due to competition for cytochrome p450. Definite risk of severe adverse affects and toxicity.

*Thyroid medications: if used simultaneously patients must be carefully monitored <ref>Gullikers, K.P., Panciera, D.L., 2002. Influence of various medications on canine thyroid function. Compendium of Continuing Education for the Practicing Veterinarian 24, 511-521</ref>

*'''Thyroid medications''': if used simultaneously patients must be carefully monitored <ref>Gullikers, K.P., Panciera, D.L., 2002. Influence of various medications on canine thyroid function. Compendium of Continuing Education for the Practicing Veterinarian 24, 511-521</ref>

*Inhibitors of cytochrome p450, including other SSRI drugs, ketoconazole and cimetidine.  

*Inhibitors of cytochrome p450, including other SSRI drugs, ketoconazole and cimetidine.  

*Drugs which lower seizure threshold (eg. phenothiazines such as acepromazine or chlorpromazine).

*Drugs which lower seizure threshold (eg. phenothiazines such as acepromazine or chlorpromazine).

Any adverse reaction should be reported via the NOAH reporting system.

Any adverse reaction should be reported via the NOAH reporting system.

===Drug withdrawal===

===Drug Withdrawal===

In humans, sudden withdrawal of SRI/SSRI/TCA drugs is associated with dysphoria, agitation, increased anxiety, relapse of psychiatric symptoms and, in some cases discontinuation syndrome<ref>Haddad, P.M., Anderson, I.A. (2007) Recognising and managing antidepressant discontinuation symptoms. Advances in Psychiatric Treatment. 13, 447-457</ref>. It is recommended that, unless otherwise indicated by drug monographs, withdrawal should be gradual. Typically a period of 1 week per month of treatment is allowed for withdrawal. This is divided into three periods of equal length with three dose decreases to 75% of original dose, followed by 50% of original dose and finally 25% of original dose.

In humans, sudden withdrawal of SRI/SSRI/TCA drugs is associated with dysphoria, agitation, increased anxiety, relapse of psychiatric symptoms and, in some cases discontinuation syndrome<ref>Haddad, P.M., Anderson, I.A. (2007) Recognising and managing antidepressant discontinuation symptoms. Advances in Psychiatric Treatment. 13, 447-457</ref>. It is recommended that, unless otherwise indicated by drug monographs, withdrawal should be gradual. Typically a period of 1 week per month of treatment is allowed for withdrawal. This is divided into three periods of equal length with three dose decreases to 75% of original dose, followed by 50% of original dose and finally 25% of original dose.

==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.

:*Stereotypy/compulsive disorders such as [[Acral Lick Dermatitis|acral lick dermatitis (ALD)]], [[Feline Grooming Disorders|compulsive grooming]] <ref>Thoren, P., Asberg, M. & Cronholm, B. (1980). Clomipramine treatment of obsessive-compulsive disorder. Archives of General Psychiatry 37, 1281–5.</ref><ref>Flament, M. F., Rappoport, J. L. & Berg, C. J. (1985). Clomipramine treatment of childhood obsessive compulsive disorder. A double-blind controlled study. Archives of General Psychiatry 42, 977–83.</ref><ref>Ananth, J. (1986). Clomipramine: an anti-obsessive drug. Canadian Journal of Psychiatry 31, 253–8.</ref><ref>Perse, T. (1988). Obsessive-compulsive disorder: A treatment review. Journal of Clinical Psychiatry 49, 48–55.</ref><ref>McTavish, D. & Benfield, P. (1990). Clomipramine: an overview of its pharmacological properties and a review of its therapeutic use in obsessive-compulsive behavior and panic attack. Drug 39, 136–53.</ref><ref>Overall, K. L. (1994). Use of clomipramine to treat ritualistic motor behavior in dogs. Journal of the American Veterinary Medical Association 205, 1733–41.</ref><ref>Hewson, C. J., Luescher, A., Parent, J. M., Conlon, P. D. & Ball, R. O. (1998b). Efficacy of clomipramine in the treatment of canine compulsive disorder. Journal of the American Veterinary Medical Association 213, 1760–6.</ref><ref>Moon-Fanelli, A. A. & Dodman, N. H. (1998). Description and development of compulsive tail chasing in terriers and response to clomipramine treatment. Journal of the American Veterinary Medical Association 212, 1252–7.</ref><ref>Dodman, N. H., Donnelly, R., Shuster, L., Mertens, P. & Miczek, K. (1996). Use of fluoxetine to treat dominance aggression in dogs. Journal of the American Veterinary Medical Association 209, 1585–7.</ref><ref>Seksel, K. & Lindeman, M. J. (1998). Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats. Australian Veterinary Journal 76, 317–21.</ref>

:*Stereotypy/compulsive disorders such as [[Acral Lick Dermatitis|acral lick dermatitis (ALD)]], [[Feline Grooming Disorders|compulsive grooming]] <ref>Thoren, P., Asberg, M. & Cronholm, B. (1980). Clomipramine treatment of obsessive-compulsive disorder. Archives of General Psychiatry 37, 1281–5.</ref><ref>Flament, M. F., Rappoport, J. L. & Berg, C. J. (1985). Clomipramine treatment of childhood obsessive compulsive disorder. A double-blind controlled study. Archives of General Psychiatry 42, 977–83.</ref><ref>Ananth, J. (1986). Clomipramine: an anti-obsessive drug. Canadian Journal of Psychiatry 31, 253–8.</ref><ref>Perse, T. (1988). Obsessive-compulsive disorder: A treatment review. Journal of Clinical Psychiatry 49, 48–55.</ref><ref>McTavish, D. & Benfield, P. (1990). Clomipramine: an overview of its pharmacological properties and a review of its therapeutic use in obsessive-compulsive behavior and panic attack. Drug 39, 136–53.</ref><ref>Overall, K. L. (1994). Use of clomipramine to treat ritualistic motor behavior in dogs. Journal of the American Veterinary Medical Association 205, 1733–41.</ref><ref>Hewson, C. J., Luescher, A., Parent, J. M., Conlon, P. D. & Ball, R. O. (1998b). Efficacy of clomipramine in the treatment of canine compulsive disorder. Journal of the American Veterinary Medical Association 213, 1760–6.</ref><ref>Moon-Fanelli, A. A. & Dodman, N. H. (1998). Description and development of compulsive tail chasing in terriers and response to clomipramine treatment. Journal of the American Veterinary Medical Association 212, 1252–7.</ref><ref>Dodman, N. H., Donnelly, R., Shuster, L., Mertens, P. & Miczek, K. (1996). Use of fluoxetine to treat dominance aggression in dogs. Journal of the American Veterinary Medical Association 209, 1585–7.</ref><ref>Seksel, K. & Lindeman, M. J. (1998). Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats. Australian Veterinary Journal 76, 317–21.</ref>.

:*Aggression where anxious apprehension is an obstacle to treatment

:*Aggression where anxious apprehension is an obstacle to treatment.

:*[[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==

<references/>

<references />

 

 

 

[[Category:Pharmacological Approach to Problem Behaviour]]

[[Category:Pharmacological Approach to Problem Behaviour]]