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Abstract 176 - .’ SUJOIARY AND CONCLUSION Trioyolio anti-depressants have beoome the drugs of choice for treatment of depression, partioularly endogenous depression. Characterized by severe depressed ” affeot and signifioant dienoephalio signs inoluding insomnia , anorexia, weight loss, deoreased energy and deoreased libido. The presenoe.or absenoe of a preoipitating faotor or oause is not of sign1fioanoefor indioation of TeA use. Evidenoe olearly suggests that presence of both a signifioant affeotive oo~onent and physioal signs of depression assures a good ohanoe for TeA effioaoy. By Diagnostio olassifioation , TeA are indi- Cated in unipolar depressive episodes , depressive episodes of bipolar patients and involutional melanoholia. TCA are not indioated for normal grief reaotions or situational reaotive ’depressions (Woolley et al., 1979). Among the six available TCA drqs (Table 4) , there is no one that olearly dominates the others in terms of efficaoy. Thus all six agents should be oonsidered to be equally effeotive anti-depressants. There are two other faotors, however , that must be oonsidered when choosing a speoifio TCA for a partioular patients I , - 177 - .•..’. , (1) Among adverseJHtferenoes, the only olinioal significant differenoe is the degree of sedation. Table 4 ranks the TeA drugs as to their relative degree of sedation. Por depression oharaoterized by marked degree of anxiety ,restlessness paoing and insomnia, it might be useful to take advantage of the sedative effect,for such a,patiettt doxeptn or amitriptyline would be the frist ohoioe. (2) The other importBnt factor in choosing a TCA for a patient is the patient’s past history of response and adverse reactions to TCA drugs. There is good evidence to suggest that some patients will respond best to amitriptyline subclass of TCA wk11e other patients will respona best to the imipramine subo1ass. TCA drugs can be dosed once daily , preferably at bed time. Effioacy of TCA drugs dosed once daily versus diVided dosage is the same and bas Ej,dvantagesof inoreased compliance , decreased adverse effects and decreased cost.(Burrows, 1983). Adverse effects of tricyclic anti-depressants include anticholinergic effects (dry mouth, blurred near vision, constipation, urinary retention) are frequent and often severe with TCA therapy, much more than with neuroleptic drugs. Pre-existing, medical conditions such as glaucoma, - 178 - Table4,a : Acute D.se Drug Sedation q/da,. Maintenance Dose. Amitriptyline. High 150 - 300 75 - 150 Doxepin. High 150 - 300 75 - 150 Imipramine. Moderate 150 - 300 75 - 150 Nortriptyline. Moderate 100 - 200 50 - 100 Desipramine. Modera’l;e 150 - 300 75 - 150 Protriptyline. Low 30 - 60 20 - 40 Table (4,a): Tricyclic anti-depressant degree of sedation and dosage level • .’ constipation and prostatiohyPertrophy must be identified and oonsidered when using TOA. Anticholinergic effects are direotely related to dose , but must often be tolerated sinoe treatment of the depression is the more important goal (Wolley et al., 1979). Cardiovascular effects are of sign1fio nt clinioal importance. Ortaostatic hypotension, or dizziness upon assuaing an ereot postures is oommon espeoially during the first few weeks of treatment. Patients - 179 t’” ””. should be cautioned about this effeot and should be told to rise slowly from a sitting or li~ position VI if they feel faint during initial TeA treatment. Use of TCA drugs in pre-existing arrh7thm1as or oongestive heart failure is a relative’oontraindioation , sinoe these oonditions may be signifioantly aggravated (Burrows, 1983). On the other h~d , the most signifioant interaction of TCA is with (-guanethidine, sinoe TCA drugs block the effect of guanethidine. Other anti-hypertensive agents should be used in the presence of TCA. The most classic interaction desoribed in the literature is TCA MAOI combinations produoing hypertensive oris is and death. T)1s interaction is not absolutely oontraindioated , however,sinoe a TCA - MAol oombination is being used clinically for treatment - resistive depression. Obviously, the presoriber of this combination must be one who is thoroughly fimiliar with these egents (Wolley et al •• 1979). The last major group of TCA interactions is with’ drugs which also possess significant anticholinergic activity. It is not uncommon for a patient to be betaking . - 180 - a neuroleptic drug such as c:hlol!Jromazine , an antiparkinson agent such as trihexyphenidyl along wi th a TCA. Anti-cholinergic activity is additive and may lead to severe anticholinergic effeots and possible C.N.S. toxicity. Other drugs and souroes of antioholinergic activity include antispasmodics , OTC sleeping preparation and OTC cold remedies (Wolley etal.,1979). Contraindication and Precautions : (1) C-a-rd-io-v-as-cu-l-ar- I • Acute myocardial infarction-wait 1IlIlItu/healed. • Presence of atrioventrioular or bundle branch block may require either inadequate doses or ’0.,,’ frequent monitoripg. • Presenoe of frequent or multifooal premature oontraotions. Lower doses of trioyolios may deorease frequenoy but higher doses may inorease vulnerable period. • Presence of unexplained blook-out these often represent short runs of ventrioular arrhythmias. - 181 - • Any state of obtunded consciousness. • Elderly patients treated with anticholinergio drugs for parkinsons disease or other indications - reduce or eliminate other drugs. • Patients with seizures - careful attention to anticonvulsant treatment program. (3) !~enCl: • During early pregnanoy - consider abortion. • Alcohol. Antihypertensives of sympatholytio type. sympathomimetics • MAO inhibitor. Antioholinergics adjust doses or change drugs. (Hollister et al., 1978). .’ - 182 - Table 4.b I Prinoiples in the use of anti-depressants a. EOT has more proof of its effioacy. espeoially in treating depression. than any other treatment in psyohiatry it may lower morbidity and mortality and alter the nat- ’0.’, ural history of the disorder. b~ Psyohotherapyof whatever type that is deemed suitable for specific patient. c. Social intervention to help patient cope better. a. Amitriptyline is suitable first ohoioe. assuming most depressions are based on serotonergic det.iciency. b. Imipramine or desipramine should be tried if amitriptyline fails • assuming the depression is based on noradrenergic deficiency. o. ~ailure of trioyclios should warrant use of MAO inhibitors, whioh may safely be added in small increments; if response is obtained. trioyclics may be phased out to use if MAO inhibitor alone does the job. ””,’ - 183 - Cont. Table l,b. d. Past experience of the patient, both in teras of therapeutic and side effects is the best guide to selection of”drJi8. a. Wide variations in plaslll&concentrations of drugs among different patients preTent ~ ”standard” dose. b. Except in the elderly or children a dose of 150 mg!day should be the target; a few patients may need less, but more will need additional doses , perhaps up to 300 mg/ day or more • c. Side effects, principally sedation or anticholinergic effect lII&ylimit dose. a. SIII&11initial doses with rapid incre ••nts of 25 mg/day to target of 150 mg/day by the end of frist week. b. A single evening dose lII&ybe feasible when the dose is 150 mg/day. c. Readjust dose at the end of second week and again at the end of thrid week depending on the patients clinical response and side ,ffeots. ””,’ · - 184 - Cont. Table 4,b • d. If no discernible response at the end of three weeks , reconsider diagnosis, choice of drug, and dose. 5- M-a-in-te-n-an-ce-- treatme-n-t:-- a. Best guide is patients natural history of disorder. b. Maintenance dose may.. be much lower than full therapeutic dose ; to the’least amount that will retain remission ; alert family and friends to signs of rel apse. c. Ultimately a drug-free period may be considered. |