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| | 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. |
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| − | ==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>==
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| − | The main adverse effects of this class of drugs is mediated through their effect on histamine and Ach receptors, as summarised in the table below.
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| − | {| class="wikitable"
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| − | |-
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| − | ! H<sub>1</sub> Blockade !! Ach (Muscarinic) Blockade
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| − | |-
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| − | | Sedation, hypotension, increased appetite, weight gain, anti-allergic activity || Delirium, hyperthermia, insomnia, seizure induction, tachycardia, constipation, decreased bronchial secretion, blurred vision, narrow angle glaucoma (exacerbation), photophobia, dry mouth
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| − | |}
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| − | Amitriptyline also antagonises α2-adrenoceptors, which can lead to agitation and tachycardia.
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| − | TCAs can also cause loss of libido (breeding animals) and mild corneal drying. They can cause galactorrhea through increased prolactin secretion (especially in cats). TCAs that predominantly alter noradrenaline re-uptake inhibition may predispose patients to sudden and violent emotional reactions including aggression and should be used with care in aggression cases.
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| − | There are large differences in selectivity of re-uptakje inhibitor drugs, as can be seen in the following table.
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| − | {| class="wikitable"
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| − | ! Drug !! Class !! 5-HT:NorAdrenaline Blocking ratio !! H<sub>1</sub> Blockade !! Ach (Muscarinic) Blockade
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| − | |-
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| − | | Amitriptyline || TCA || 1:4 || +++ || +++
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| − | |-
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| − | | Clomipramine || TCA || 5:1 || ++ || ++
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| − | |-
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| − | | Fluoxetine || SSRI || 15:1 || || +
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| − | |-
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| − | | Fluvoxamine || SSRI || 150:1 || || +
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| − | |-
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| − | | Sertraline || SSRI || 150:1 || || +
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| − | |}
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| − | The blocking ratio indicates the relative effect of the agent on reuptake of 5-HT vs. noradrenaline. Fluoxetine is 3 times more selective for 5-HT than clomipramine. Clomipramine was the first TCA whose ratio favours 5-HT 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.
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| − | '''Caution should be taken if the animal suffers from any of the following pre-existing medical conditions:'''
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| − | *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>
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| − | *Diabetes: increases hyperglycaemia
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| − | *Glaucoma (closed angle type)
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| − | *Impaired liver function (TCAs metabolised by liver)
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| − | *Hyperthyroidism (enhanced response to TCAs)
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| − | *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>.
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| − | '''Care should be taken if used in conjunction with any of the following drugs, which may interact and cause adverse effects:'''
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| − | *Morphine: enhanced analgesia and respiratory depression.
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| − | *MAOIs: risk of serotonin syndrome, advise washout period of 2-3 weeks between treatment with these drugs.
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| − | *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.
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| − | *SSRIs: Fluoxetine inhibits Cytochrome p450, leading to toxic levels of TCA. Cimetidine also has this effect.
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| − | *Fibre rich diets reduce availability of TCAs.
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| − | *Thyroid medications: can interfere, therefore if simultaneously used 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>
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| − | If the drug is overdosed/combined with an inappropriate drug (see above) an increased sedation and degree of adverse effects as listed will be seen. If the drug dose is persistently high or the drug is combined with an MAOI, serotonin syndrome is a possible consequence:
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| − | *Gastrointestinal distress
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| − | *Head pain
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| − | *Agitation
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| − | *Increased heart rate, body temperature, respiratory rate
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| − | *Muscular rigidity
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| − | *Convulsions
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| − | *Coma
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| − | *Death
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| − | Any adverse reaction should be reported via the NOAH reporting system.
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| | ==Fluoxetine== | | ==Fluoxetine== |