الفهرس 
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Abstract
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SUJOIARY AND CONCLUSION
Trioyolio anti-depressants have beoome the drugs
of choice for treatment of depression, partioularly
endogenous depression. Characterized by severe depressed
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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
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(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,
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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 •
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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
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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
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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
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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.
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• 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).
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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-
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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.
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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.
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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.