A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

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, tryptophan or 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 fluoxetine for at least five weeks
before using MAOI because of its particularly long halflife
(about two days).
• The action of warfarin is probably enhanced by
fluoxetine and paroxetine.
• There is antagonism of anticonvulsants.
• Fluoxetine raises blood concentrations of haloperidol.
Psychotherapy
Significant symptoms
persist after 6 weeks
Diagnosis of unipolar
depression
Psychotherapy
and medication
Medication
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.
Duloxetine inhibits NA and 5HT reuptake.
Add medication
Evaluate response
to medication after
3–4 weeks
TRICYCLICS AND RELATED ANTIDEPRESSANTS
(TCAs)
Uses
These include the following:
Partial response
Continue same
treatment
No response
Advance dose
as tolerated
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. imipramine has some efficacy in nocturnal enuresis.
Symptoms resolving
Evaluate response
to medication after
6–8 weeks
Symptoms persist
Go to second phase
of treatment
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 Physician Vol 36 No 7, 2000. Copyright 2000
Turner White Communications, Inc.)
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 amitriptyline,
dosulepin and doxepin. These are more appropriate
for agitated or anxious patients than for withdrawn or apathetic
patients, for whom imipramine or nortriptyline,
which are less sedative, are preferred. Protriptyline is 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 multicentre
collaborative study organized by the World Health
Organization failed to demonstrate any relationship whatsoever
between plasma amitriptyline concentration and clinical
effect.