A Textbook of Clinical Pharmacology and Therapeutics

118 MOOD DISORDERS

3.Epilepsy can be precipitated.
4.They are usually non-sedating, but may cause insomnia
and do not usually cause orthostatic hypotension.
5.All antidepressants can cause hyponatraemia, probably
due to induction of inappropriate antidiuretic hormone
secretion, but it is reported more frequently with SSRIs
than with other antidepressants.

Contraindications

These include the following:

• hepatic and renal failure;


• epilepsy;


• manic phase.

Drug interactions

• Combinations of SSRI with lithium,tryptophanor MAOIs
  may enhance efficacy, but are currently contraindicated
  because they increase the severity of 5HT-related toxicity.
  In the worst reactions, the life-threatening 5HT syndrome
  develops. This consists of hyperthermia, restlessness, tremor,
  myoclonus, hyperreflexia, coma and fits. After using MAOIs,
  it is recommended that two weeks should elapse before
  starting SSRIs. Avoid fluoxetinefor at least five weeks
  before using MAOI because of its particularly long half-
  life (about two days).


• The action of warfarinis probably enhanced by
  fluoxetineandparoxetine.


• There is antagonism of anticonvulsants.


• Fluoxetineraises blood concentrations of haloperidol.

SEROTONIN-NORADRENALINE REUPTAKE

INHIBITORS AND RELATED ANTIDEPRESSANTS

Venlafaxine: A potent 5HT and NA uptake inhibitor that

appears to be as effective as TCAs, but without anticholinergic

effects. It may have a more rapid onset of therapeutic action

than other antidepressants, but this has yet to be confirmed. It

is associated with more cardiac toxicity than the SSRIs.

Duloxetineinhibits NA and 5HT reuptake.

TRICYCLICS AND RELATED ANTIDEPRESSANTS

(TCAs)

Uses

These include the following:

1. depressive illnesses, especially major depressive episodes
   and melancholic depression;
   2.atypical oral and facial pain;
   3.prophylaxis of panic attacks;
   4.phobic anxiety;
   5.obsessive–compulsive disorders;
   6.imipraminehas some efficacy in nocturnal enuresis.

Although these drugs share many properties, their

profiles vary in some respects, and this may alter their use in

different patients. The more sedative drugs include amitripty-

line,dosulepinanddoxepin. These are more appropriate

for agitated or anxious patients than for withdrawn or apa-

thetic patients, for whom imipramine or nortriptyline,

which are less sedative, are preferred. Protriptylineis usually

stimulant.

Only 70% of depressed patients respond adequately to

TCAs. One of the factors involved may be the wide variation in

individual plasma concentrations of these drugs that is

obtained with a given dose. However, the relationship between

plasma concentration and response is not well defined. A mul-

ticentre collaborative study organized by the World Health

Organization failed to demonstrate any relationship whatso-

ever between plasma amitriptyline concentration and clinical

effect.

Diagnosis of unipolar

depression

Psychotherapy

and medication

Continue same

treatment

Advance dose

as tolerated

Go to second phase

of treatment

Evaluate response

to medication after

3–4 weeks

Evaluate response

to medication after

6–8 weeks

Significant symptoms

persist after 6 weeks

Psychotherapy

Symptoms resolving Symptoms persist

Partial response No response

Add medication

Medication

Figure 20.1:General algorithm for the initial phase of treatment
of depression. When symptoms persist after first-line treatment,
re-evaluate the accuracy of the diagnosis, the adequacy of the dose
and the duration of treatment before moving to the second
phase of treatment. (Redrawn with permission from Aronson SC
and Ayres VE. ‘Depression: A Treatment Algorithm for the Family
Physician’,Hospital PhysicianVol 36 No 7, 2000. Copyright 2000
Turner White Communications, Inc.)