Treatment resistant depression

2. Augmenting strategies

One antidepressant used with an augmenting agent (non-antidepressant) to exhibit a synergistic effect (increasing efficacy of antidepressant) or enhancing tolerability by inhibiting side effects e.g. lithium

Lithium is used to treat bipolar patients to control manic symptoms
Also proven to be effective in adjunct therapy to standard antidepressant in ACUTE PHASE of MAJOR DEPRESSION

Effects of lithium augmentation

Increases response in unresponsive patients
Initiate response in unresponsive patients when used with TCA’s, SSRI’s, MAOI’s and SNRI’s e.g. venlafaxine
Effective in continuation treatment phase to prevent relapse
Animal studies have shown that lithium enhances serotonin neurotransmission
Neuroendocrine studies supports this by augmenting the function of serotonergiv system
Effects of anticonvulsant augmentation
Anticonvulsants e.g. valproate, carbamazepine, and lamotrigine combined with classical antidepressants: well tolerated and effective in treatment resistant depressed patients
Venlafaxine combined with carbamazepine has proved to be effective in the treatment of depressed patients not responding to monotherapy with venlafaxine

Effects of antipsychotic augmentation

Atypical antipshychotics (e.g. aripriprazole, olanzapine, quetiapine, risperidone) deemed beneficial in patients exhibiting treatment resistant depression without psychotic features

Milder side effect profile compared to typical antipsychotics

What does NICE say?

Monitor patients weight (weight gain particularly in olanzapine), lipid, and gluose levels (diabetes, hyperglycaemia particularly in olanzepine, quetiapine, risperidone)

Targets DA and NA pathways
By targeting DA pathway : effects pleasure, motivation, psychomotor activity, insomnia, agitation, appetite
By targeting NA pathway:
By affecting 5HT 2A and 5HT 2C receptors : overcome side effects of SSRI’s such as agitation, insomnia, sexual dysfunction

1. Switching strategies

This involves treatment being switched from within a certain class of antidepressants, between different classes of antidepressants, ECT, or psychotherapy

What does NICE say?

If response is absent/minimal for after 3-4 weeks of treatment,

Increase levels of support (telephone consultations, and face to face)
Then consider increasing dose if there are no significant s/e’s (if there are significant s/e’s then switch to another antidepressant)
Advantage of switching from one class to another : weak evidence
Switching can usually be achieved in a week in drugs with short ½ lives

Caution must be taken of switching:

From fluoxetine to other antidepressants (due to fluoxetines long ½ life)
From Fluoxetine or paroxetine to a TCA
Non reversible MAOI : requires fortnight wash out period (during this no other antidepressant can be prescribed

3. Combination therapies

Serotonergic activity

2 agents to create pharmacological synergy
SSRI’s inhibit reuptake of serotonin at the synapse
Surge of serotonin causes stimulation of 5-HT”A receptors cause insomnia and agitation
Blockade of this and inhibition of serotonin = increased serotonin at the synapse
Therefore increase the dose is achievable and increase efficacy e.g. sertraline, and trazodone

Noradrenergic strategy

No particular evidence

I'm a paragraph. Click here to add your own text and edit me. I’m a great place for you to tell a story and let your users know a little more about you.

As shown in the treatment for depression, when patients fail to respond to monotherapy, certain strategies must be adopted by the practitioner. Failure to respond to a 2nd antidepressants may require either:

Combination therapy

Augmenting therapy

The goals of therapy are to:

Enhance the repsonse rate of current antidepresants
Acquire FULL remission (i.e. the complete absence of all symptoms of depression).
Overcome treatment resistant depression

Although some patients show a response, this does NOT mean they are CURED or in REMISSION

2/3 of depressed patient will show response to some extent however 1/3 will be completely unresponsive