Download Management of treatment- resistant depression

Clinical Focus
Continuing education and moving points in medicine
Module 21: Brain disease
Management of treatmentresistant depression
Many patients who do not respond to initial treatment for depression will
subsequently find remission when prescribed alternative or supplemental
antidepressants, write Clare Shields and Declan Lyons
No 10 Dec 2014/Jan 2015
and information on the treatment steps in the management of
depression.3
According to this trial, the first choice in the treatment of
depression is an SSRI. A typical choice would be citalopram 20mg
or escitalopram 10mg. If a patient does not respond to the initial
antidepressant or cannot tolerate it, it is recommended to switch
antidepressant class. When switching class, you should taper and
then stop the initial antidepressant and start the new medication.
There are many choices available when switching antidepressant class. The most commonly prescribed would be the
serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine,
followed by atypical antidepressants such as mirtazapine and
bupropion.
Tricyclic antidepressants such as amitriptyline and dothiepin
are less commonly prescribed and tolerability issues, often arising
from anticholinergic side-effects, may be relevant. Monoamine
oxidase (MAO) inhibitors, for example, phenelzine, are another
option.
The role of venlafaxine when switching from an SSRI is well
researched. A meta-analysis compared switching from an SSRI to
another SSRI or to venlafaxine. It found remission was obtained
in more patients who received venlafaxine than a different SSRI.4
Changing to atypical antidepressants from an SSRI shows similar efficacy to switching to another SSRI.5
If a patient is tolerating the antidepressant well and has some
symptom relief but it is not yet satisfactory, augmentation is
recommended as first-line management. Augmentation agents
include second generation antipsychotics such as quetiapine, aripiprazole and olanzapine. Lithium or a second antidepressant, for
example, mirtazapine or bupropion can also be prescribed. Other
agents include buspirone and triiodothyronine.
There is little difference in the efficacy of these medications,3
therefore, it is important to take into account the past medical
history of the patient, their previous treatment record, patient
preference and cost, safety, side-effects and interactions of the
medications when prescribing. It is also reasonable to switch antidepressant in this scenario.6
It is accepted too that augmentation of an antidepressant that
WIN Vol 22
Mental illness affects one in four people in their lifetime.1 Mood
disorders are the most common mental illnesses and depression is
the fourth highest cause of disability worldwide. It is an extremely
common presentation to primary care with only upper respiratory
tract infections and hypertension presenting more frequently.2
A significant number of people with depression do not respond
to the initial treatment. In one trial, only 37% of patients
obtained remission with citalopram (a selective serotonin reuptake inhibitor – SSRI) alone.3 Treatment-resistant depression does
not have a standardised definition but is widely considered to be
a failure to respond satisfactorily to two trials of antidepressant
monotherapy.
It is important to be aware of the steps in the treatment plan
for depression, including the different antidepressant classes
and augmentation agents, the availability and benefits of
psychotherapy, and the social supports surrounding the patient. It
is also vital to educate and give appropriate information about the
treatment options available, such as electroconvulsive therapy
(ECT), if a patient requires inpatient care and treatment.
Important considerations
When making a diagnosis of treatment-resistant depression,
it is important, firstly, to establish if the diagnosis of depression
is correct. Other psychiatric diagnoses such as anxiety disorders,
dysthymia, personality disorders, adjustment disorders and alcohol and drug abuse should be ruled out. It is also important to
ensure that there is no underlying medical disorder, for example, Parkinson’s disease, multiple sclerosis, dementia or thyroid
disorders.
The importance of compliance to medications should be
explored with patients and they should be prescribed an adequate trial of an antidepressant. This would usually be for six to 12
weeks, however, if there is little response after four to six weeks,
it is advised to move to the next treatment step.
Biological treatment
The STAR*D trial, (Sequenced Treatment Alternatives to Relieve
Depression), which was a collaborative study on the treatment of
depression, completed in 2006 and funded by the National Institute of Mental Health in the US, provides much of the evidence
WIN Vol 22
No 10 Dec 2014/Jan 2015
60 CLINICAL FOCUS
has not had any effect can be tried as first-line rather than switching class. In both cases there is little difference in the outcomes
between switching and augmentation in treatment-resistant
depression.7
The STAR*D trial has shown that 67% of patients who fail to
respond to an initial course of citalopram will achieve remission
with up to four courses of successive treatment. Prognosis is
worse for patients with prominent anxiety symptoms or a comorbid anxiety disorder. Lack of social support also negatively
impacts on patients.
Psychotherapy
Psychotherapy may be employed as an alternative to medication in mild to moderate depression and can be useful in
severe depression in combination with medications. It is particularly beneficial for relapse prevention. Models of therapy
include cognitive behavioural therapy or interpersonal therapy.
However, the availability of psychotherapy is frequently a limiting factor.
Research has also shown that psychotherapy is more successful
in certain patient groups. This includes patients with higher levels of education and patients who have a family history of mood
disorders.8 A 12-week study compared CBT to an antidepressant
(venlafaxine, bupropion or sertraline) in patients who did not
obtain symptom relief with citalopram. It showed similar rates
of remission with both treatments. Similar numbers also stopped
each treatment due to side-effects or incompatibility.8
Social supports
It is important to explore with patients the social supports
available to them including family and friends. Education regarding depression and its symptoms is also vital for patients and their
families.
Organisations such as Aware (www.aware.ie) offer a range of
services including information, education and formal supports
such as Aware’s Life Skills programme. Patients and families can
access these services online or can participate in support meetings through the nationwide network of local groups.
Other useful services include the crisis support agency, Samaritans (www.samaritans.org) and Pieta House (www.pieta.ie), an
organisation with multiple locations around the country, which
helps to prevent suicide and self-harm.
Referral and ECT
If the above treatment steps have failed, referral to a psychiatrist should be considered. It is recommended for patients who
do not respond to between two and four treatment trials. Referral is also required if psychosis, suicidal ideation or catatonia are
present.
One treatment available if the patient is admitted to hospital is ECT. It can be particularly useful in patients with psychotic
depression and is first-line when persistent suicidal ideation is
present, there is dehydration or weight loss due to refusal to eat
or malignant catatonia.9
It is the most effective treatment in patients with major depression and can be considered first-line for patients with severe
treatment-resistant depression.10 Six to eight treatments are
usually required to achieve remission and two treatments are typically given per week. It is not available in all psychiatric centres
in Ireland.
ECT has perhaps an unjustifiably negative public image, focusing particularly on concerns about adverse effects on cognitive
function. However, it has not been shown to have an effect on
long-term cognition.
Conclusion
Depression is a very common presentation, affecting one in
four people in their lifetime. It is important to regularly review
affected patients in relation to symptoms and side-effects of the
medications. We need to emphasise the importance of persisting
with treatment trials. These patients require reassurance that
they will not be abandoned and they should be encouraged to
have faith in the treatment.
Treatment-resistant depression can be challenging to manage
and healthcare professionals need to draw on all the resources
available to them and remain up to date regarding the latest
developments in the management of this condition.
Clare Shields is a psychiatry registrar and Declan Lyons is a consultant psychiatrist
at St Patrick’s Hospital, Dublin
References
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comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry. 2005;62(6):617-27
2. Cooke G, Valenti L, Glasziou P, Britt H. Common general practice presentations and
publication frequency. Australian family physician. 2013;42(1-2):65-8
3. Rush AJ, Trivedi MH, Wisniewski SR et al. Acute and longer-term outcomes in depressed
outpatients requiring one or several treatment steps: a STAR*D report. The American journal of psychiatry. 2006;163(11):1905-17
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RM. ECT in treatment-resistant depression. The American journal of psychiatry.
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