Case Study 10:
Depression
September 2000
Scenario
Mrs Bond is a 46 year old who is agitated, and complains of appetite loss and
low mood over the previous two months. During the examination she is teary,
complains of inability to sleep, and loss of interest in work and leisure
activities. She has been stressed and unable to function at work. The patient
denies any suicidal thoughts. Physical examination and other investigations
are normal, and the diagnosis of major depression is made. You agree with
Mrs Bond to schedule a series of appointments for counselling. Because of
the severity of the symptoms, which meet diagnostic criteria for major
depression, you decide to initiate antidepressant therapy.
Inside
Results
In summary
In detail
page 3
page 4
Expert commentaries
Dr Bill Lyndon
page 9
A/Professor Dimity Pond
page 12
2
Case Study Results
Results in summary
1119 responses were received to this case study and the aggregate results of two hundred responses
were compiled for feedback.
Most respondents (74%) prescribed a selective serotonin reuptake inhibitor (SSRI) as
initial antidepressant therapy. Sertraline (35%) and paroxetine (21%) were the most
common. Tricyclic antidepressants (TCAs) were chosen for 11% of respondents and
nefazodone, moclobemide and venlafaxine, combined, accounted for 14%.
Over 88% of respondents indicated their choice of antidepressant was influenced by
efficacy and adverse effect profiles. Reasons specified included proven effectiveness,
past prescribing success and lower incidence of adverse effects with the SSRIs and
newer antidepressants.
Most prescribers (84%) of SSRIs would discuss the frequent adverse effects with the
patient and of these 13% would also provide management advice for adverse effects,
especially if symptoms persisted after 1-2 weeks. All the prescribers of nefazodone,
venlafaxine and moclobemide would provide the patient with specific adverse effects.
Half of these prescribers would also discuss management of adverse effects. The
prescribers of TCAs would discuss the common adverse effects and included the
warning to avoid alcohol and /or caution about driving machinery. Other important
information given to the patient included delay in onset of action, timeframe of
treatment, and importance of compliance.
The majority of respondents would not prescribe any other drug therapy (64%). Of the
36% who would prescribe other drug therapy, 32% would prescribe a concomitant
benzodiazepine. Only 4% indicated they would change antidepressant therapy if
initial choice gave a poor response.
Most respondents would maintain antidepressant therapy for a minimum of six months after initial
response.
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Results in detail
Question 1
What would you prescribe as initial antidepressant therapy?
Choice of antidepressant and starting doses are shown in the table below.
Drug
Brand name
Starting dose
SSRIs
Sertraline1
Zoloft
Citalopram2
Cipramil
Paroxetine1
Aropax
Fluoxetine
Lovan, Prozac, Zactin
Auscap, DBL or SBPA
Fluoxetine, Fluohexal
Luvox, Faverin 100
Fluvoxamine
Other newer antidepressants
Nefazodone2
Serzone
Venlafaxine
Efexor XR
Reversible monoamine oxidase A inhibitor
Moclobemide
Aurorix, Arima,
DBL Moclobemide
Tricyclic antidepressants
Dothiepin
Dothep, Prothiaden
Nortriptyline
Trimipramine
Amitriptyline3
Allergon
Surmontil
Endep, Tryptanol,
Tryptine, Amitrol
Doxepin3
Deptran, Sinequan
Other antidepressant therapy
Mianserin
Lumin, Tolvon
Other drug therapy
Murelax, Serepax,
Oxazepam5
Alepam
1
2
3
4
5
25mg daily
25mg–50mg daily
50mg daily
50mg-100mg daily
10mg daily
10mg-20mg daily
20mg daily
10mg daily
10mg-20mg daily
20mg daily
20mg daily
1
2
30
2
1
2
8
3
1
17
5
50mg daily
100mg daily
1
<1
50mg twice daily
100mg twice daily
150mg twice daily
300mg daily
75mg XR daily
150mg daily
1
2
1
1
3
<1
150mg twice daily
300mg twice daily
300mg daily
600mg daily
2
2
<1
<1
25mg daily4
50mg daily
75mg daily
75mg-150mg daily
75mg daily
75mg daily
50mg daily
3
1
4
1
<1
<1
<1
50mg daily
<1
30mg daily
<1
15mg three times daily
One respondent gave a choice of either sertraline or paroxetine
One respondent gave a choice of either citalopram or nefazodone
One respondent chose either doxepin or amitriptyline
Five respondents would rapidly increase dose within a week to 75-150mg
One respondent chose oxazepam as initial therapy before prescribing an antidepressant
4
Percentage
respondents
<1
Question 2
What influenced your choice of initial antidepressant drug therapy?
Over 88% of respondents indicated their choice of antidepressant was influenced by efficacy and
adverse effect profiles. The following table shows the reasons why prescribers chose one antidepressant
over another.
Choice of initial
antidepressant
Sertraline
Paroxetine
Citalopram
Dothiepin
Moclobemide
Nefazodone
Fluoxetine
Venlafaxine
Fluvoxamine
Mianserin
Trimipramine
Nortriptyline
Amitriptyline
Doxepin
Oxazepam
Percentage
respondents*
Efficacy
35
21
11
9
5
5
5
4
2
1
1
1
1
1
1
34
18
9
7
5
5
4
3
2
1
1
1
0
0
1
Influenced by (%)
Adverse
Cost
effects
33
6
16
3
11
4
5
3
5
2
5
1
4
2
3
1
2
1
1
1
0
0
0
0
1
1
1
1
0
0
Other
reasons
18
10
3
4
1
1
2
1
1
0
1
1
0
0
0
* Several respondents gave more than one choice
Common reasons given for choice of initial antidepressant are listed below:
Efficacy
Proven effectiveness (literature or past experience)
Equal efficacy to other antidepressants
Quick onset of action
Good for agitation and/or anxiety
Adverse effect profile
SSRIs
Minimal adverse effects
Less adverse effects than TCAs
Better profile than other SSRIs
e.g. 40% of paroxetine prescribers and 24% of citalopram prescribers
Causes less agitation
Safer in overdose
Nefazodone
Minimal adverse effects
Better profile than SSRIs
e.g. of the nefazodone prescribers 55% indicated less insomnia, 27% less
agitation, and 18% less sexual dysfunction.
Safer in overdose
TCAs
Benefit of sedation
Better profile than SSRIs
e.g. less agitation
Cost
SSRIs were comparable to others
TCAs were cheaper
5
Other influences
Familiarity with prescribing the antidepressant
SSRIs were considered better for compliance because of dosage schedule and
better adverse effect profile.
Degree of sedation and anxiolytic properties
Safety in overdose.
Question 3
What would be your target maintenance dose of antidepressant?
The respondents’ choices of target maintenance doses are shown in the table below.
Antidepressant
Target maintenance dose
Sertraline
50 mg daily
50-100 mg daily
100 mg daily
100-150 mg daily
max. 200 mg daily
20 mg daily
20-40 mg daily
40 mg daily
50 mg daily
unspecified
20 mg daily
20-40 mg daily
max. 60 mg daily
20 mg daily
20-40 mg daily
40 mg daily
300 mg daily
100-300 mg daily
100-150 mg daily
150mg-300mg twice daily
200mg-300mg twice daily
75mg daily
75mg-150mg daily
150mg daily
max. 225mg daily
300mg-600mg daily
600mg daily
600mg-1200mg daily
50mg-150mg daily
100mg-150mg daily
150mg daily
150mg-200mg daily
75mg-150mg daily
150mg daily
150mg daily
75mg daily
30mg-90mg daily
Paroxetine
Citalopram
Fluoxetine
Fluvoxamine
Nefazodone
Venlafaxine XR
Moclobemide
Dothiepin
Nortriptyline
Doxepin
Amitriptyline
Trimipramine
Mianserin
Percentage
Respondents
2
18
8
3
3
11
7
1
<1
<1
8
2
1
3
1
1
<1
1
1
4
2
<1
1
2
<1
2
2
1
4
1
3
1
<1
<1
<1
<1
1
Question 4
What specific information about antidepressant therapy would you give the patient?
From prescribers of SSRIs
84% of prescribers of SSRIs would discuss common adverse effects with the patient.
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Specific adverse effects of SSRIs discussed
Gastrointestinal disturbances / nausea
Sleep disturbances / insomnia
Agitation or anxiety
Sexual dysfunction
Headache
Nervousness / tremor
Dizziness
Serotonin syndrome
**Others
Percentage respondents*
49
32
25
17
9
5
5
2
8
* Respondents may have indicated more than one adverse effect
** Several respondents indicated weight gain as an adverse effect of paroxetine
Other specific information given to patients on SSRIs
Other specific information on SSRIs
Delay in onset of action
Timeframe of treatment / time until maximum effect
Compliance & need for counselling or review
Drug interactions
Advised not to stop abruptly
Mode of action
Dosing schedule
No addiction
Caution with driving / machinery or alcohol
Other
Percentage respondents
60
33
18
15
11
12
7
7
5
7
For prescribers of nefazodone, venlafaxine & moclobemide
All respondents mentioned specific common adverse effects. Gastrointestinal adverse
effects were mentioned for nefazodone. Dry mouth and dizziness were specifically
mentioned for moclobemide. Half of the respondents commented on adverse effect
management, if problematic. Other information to be provided included delay in onset
of action, timeframe of treatment and importance of compliance.
For prescribers of TCAs
The specific adverse effects mentioned by these respondents (11%) included sedation
or drowsiness, gastrointestinal disturbances, anticholinergic effects and postural
hypotension. Of these respondents 54% advised the patient to avoid alcohol and/or
cautioned about driving machinery. Delay in onset of action, timeframe of treatment
and the need for counselling were also commonly mentioned.
7
Question 5
Would you prescribe any other drug therapy? If yes, what drug, dose and frequency?
Most respondents (64%) would not prescribe any other drug therapy. One third of the
respondents (36%) who considered prescribing other drug therapy interpreted the
question in two ways.
Concomitant therapy
Some respondents (32%) who considered co-prescribing with an antidepressant chose
benzodiazepines. The most common benzodiazepine prescribed was temazepam 10mg
at night. Two-thirds of these prescribers also stated that the length of treatment should
only be 1-2 weeks or short term to overcome initial insomnia.
Alternative therapy if poor response
A small number (4%) of respondents assumed that the question was about alternative
selection of an antidepressant if there was a poor response to the first agent chosen.
Examples of the suggested alternatives of antidepressant therapies are listed below.
Other drug therapies prescribed if poor response to initial choice
Oxazepam
Sertraline
Sertraline
Moclobemide
Moclobemide
Fluoxetine
Citalopram
Sertraline
to
to
to
to
to
to
to
to
paroxetine
paroxetine
moclobemide
fluoxetine
doxepin
nefazodone
TCA
TCA
Question 6
For how long after initial response would you expect to maintain antidepressant
therapy?
A minimum of six months was the most common length of treatment chosen. Summary of responses
are shown below.
Months of antidepressants therapy after initial response
0-3 months
3-6 months
6 months
6-12 months
12 months
12-24 months
Percentage respondents
7
14
40
29
5
3
5% of respondents gave nonspecific answers or stated the duration of treatment depended on frequency
of recurrent episodes.
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Expert commentary
Dr Bill Lyndon
Psychiatrist, Mood Disorder Unit, Northside Clinic, Sydney
Lecturer, Department of Psychological Medicine,
University of Sydney
This is a typical presentation of depression in general practice. Key points are that the symptoms meet
diagnostic criteria for depression, so treatment is required, and that the severity of symptoms and
degree of loss of psychosocial functioning are sufficient to warrant antidepressant treatment as part of
the management. The suicide risk appears low, so management in the general practice setting is
appropriate.
Question 1
What would you prescribe as initial antidepressant therapy?
There are no apparent comorbid medical or psychiatric illnesses present which might influence the
choice of antidepressant. Nearly 90% of respondents chose one of the newer antidepressants over the
tricyclics and the majority chose an SSRI. Any of the new antidepressants would have been an
appropriate first choice and it is interesting that the SSRIs were favoured over nefazodone,
moclobemide and venlafaxine. There are no apparent clinical features which would support choosing
an SSRI over the other new drugs, so other factors are clearly relevant. Choosing a tricyclic first in a
young healthy woman is not unreasonable, but the advantages of the newer drugs indicate that these are
a better first choice for most cases.
Most respondents chose an appropriate and standard starting dose. Some chose
smaller starting doses and in an agitated, anxious patient or in a patient with a past
history of antidepressant induced agitation this would be sensible. Starting with too
high a dose is to be avoided because of the added side effect burden and probable loss
of compliance. Some chose a large starting dose: for nefazodone ≥300mg, for
moclobemide of 600mg and for dothiepin ≥75mg. These starting doses would be
poorly tolerated by many patients.
Question 2
What influenced your choice of initial antidepressant drug therapy?
Most respondents accept that there is little if any difference in efficacy between the various
antidepressants and based their choice on other factors, namely safety, side effect profile, simplicity of
dosing and familiarity with the particular drug. Cost did not figure prominently, so presumably the
advantages of the new drugs are considered to outweigh the cost advantages of the tricyclics. Most
clinicians would also be aware that although the cost to the patient of TCAs is less, indirect costs as a
result of non-compliance, side effects or iatrogenic illness associated with tricyclics tend to reduce the
cost differential.
The SSRIs have varying capacities for causing agitation, insomnia and sexual
dysfunction and there is also wide individual variation among patients to develop side
effects to a particular SSRI. It is therefore difficult to generalise about the side effect
potential of a particular drug for a particular patient and clinicians should be prepared
to switch from one SSRI to another if the first choice proves unacceptable.
It is likely that those who chose a TCA did so because of the sedating properties and to avoid
worsening the patient’s insomnia. While this is reasonable, it is important to note that sleep is not
always worsened by the newer drugs; it is often improved and if there is a problem it is likely to be
temporary and appropriately managed with short term use of a hypnotic. Similarly, the new
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antidepressants often have a calming effect on anxious, agitated patients and should not be avoided for
this reason only.
The side effect of sexual dysfunction was considered by a minority of respondents. While this may not
be relevant to the majority of depressed patients in the acute phase, it is likely to become more of an
issue after recovery and may become an important reason to consider changing antidepressant.
Question 3
What would be your target maintenance dose of antidepressant?
In general, antidepressants need to be given at full dosage for maintenance treatment and not reduced.
The answers mostly are consistent with this. There was a trend for some antidepressants to be given at
higher doses during the maintenance phase, which probably reflects an expectation that for SSRIs at
least, doses would need to be increased above the starting dose to achieve remission. This trend was
more noticeable for sertraline and paroxetine than for the other SSRIs and other new antidepressants.
This suggests that doses for sertraline and paroxetine may be escalated too rapidly and unnecessarily.
For most patients on SSRIs, the starting dose will be adequate to produce response and dose increases
should not be necessary before 3-4 weeks. There is no doubt that some patients will require these
higher doses but the majority will not.
Doses given for nefazodone may be inadequate – 400-600mg will be needed for most
patients. Similarly, the doses for the TCA dothiepin are low, less than 150mg mostly,
and this would generally be considered to be subtherapeutic. It has long been
appreciated that TCAs are generally used in inadequate doses in general practice.
Question 4
What specific information about antidepressant therapy would you give the patient?
Most respondents indicated they would give appropriate advice about the
antidepressant, but the breakdown figures indicate that some important advice is not
being given. A minority only would warn about insomnia, agitation, sexual
dysfunction and abrupt discontinuation. The timeframe of response does not appear to
be adequately discussed. All patients should be informed of the delayed onset of
action and that response may not be achieved in less that 3-4 weeks or possibly 4-6
weeks. Unrealistic patient or doctor expectations of recovery may lead to noncompliance, premature discontinuation or pressure to increase doses or change drugs.
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Question 5
Would you prescribe any other drug therapy? If yes, what drug, dose and frequency?
Short-term use of a hypnotic such as temazepam can be very useful to assist with the insomnia of
depression or antidepressant induced insomnia. Most respondents accept the usefulness of this strategy.
Benzodiazepine anxiolytics were nominated by a small number of respondents only and this is
consistent with good practice. There is no history of anxiety with this patient and therefore no reason to
prescribe an anxiolytic. In particular, there are no panic symptoms and alprazolam therefore does not
have a place.
Anxiolytics may at times be a helpful addition, but the anxiety associated with depression will usually
settle quickly once treatment has commenced, even with the SSRIs. If a patient develops severe
agitation with an antidepressant, which does not settle, changing antidepressant should be considered as
an alternative to adding an anxiolytic.
Changing if poor response
This raises some interesting points of how to manage this problem. Some (4%) of respondents
volunteered that they would change to another antidepressant if the first choice was ineffective. If the
first choice is ineffective, then a second trial with a different antidepressant, preferably from a different
class, is the correct action.
There is inadequate evidence to support the efficacy of combining antidepressants and there are
significant risks of drug-drug interactions leading to delayed metabolism and potentially dangerous
serum levels (e.g. SSRIs + TCAs), as well as serotonin syndrome (combine SSRIs + MAOI, SSRI +
SSRI). Combining antidepressants is not a strategy for use in general practice and it is debatable
whether it is appropriate in psychiatric practice.
Question 6
For how long after initial response would you expect to maintain antidepressant
therapy?
Assuming this is a first episode and the patient does not suffer from recurrent
depression, then the medication should be continued for 6 months. With recurrent
depression, 6-12 months or longer, possibly indefinitely, is more appropriate. Six to12
months would also be appropriate following severe episodes with profound loss of
functioning especially if the risk of suicide is high. A significant minority of
respondents elected to continue medication for greater than 6 months, which would be
unnecessary for the patient described, provided that full remission is achieved and
there are no ongoing unresolved risk / aetiological factors.
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Associate Professor Dimity Pond
Société Professor in General Practice,
Faculty of Medicine & Health Sciences, University of Newcastle
This is a typical case in General Practice, although in real life I would like to look at
current stressors as well as noting the symptoms of depression during the first
consultation. I would also assess her for any symptoms of psychotic depression (e.g
visual or auditory hallucinations) as well as for suicidality. The presence of either
would increase the likelihood that I would refer her for specialist review.
Question 1
What would you prescribe as initial antidepressant therapy?
88% of respondents would prescribe one of the newer antidepressant agents as initial
drug therapy. I would tend to agree with them.
Question 2
What influenced your choice of initial antidepressant drug therapy?
My choice would be influenced by the superiority of the newer agents in the case of
overdose. Although this patient denies suicidality, this possibility should always be
considered in a case of major depression.
Many GPs commented on the side effect profiles of SSRIs compared with tricyclics. While SSRIs
avoid many of the unpleasant side effects of the tricyclics, such as dry mouth and drowsiness, there are
still a number of possible side effects with all the newer agents, including agitation and sexual
dysfunction, and these should be discussed with the patient. The agitation this patient is already
exhibiting might provide a rationale for prescribing one of the older more sedating tricyclics.
However, this needs to be balanced against her need to function at work and home and the risk of
suicide.
Question 3
What would be your target maintenance dose of antidepressant?
The target maintenance dose should be that which maintains the patient’s function and
keeps her as free as possible from the symptoms of depression, provided that side
effects are taken into account.
Question 4
What specific information about antidepressant therapy would you give the patient?
I believe it is essential to discuss possible side effects with the patient and refer her to
the consumer medicines information (CMI) leaflet to ask her to ring if she experiences
any symptoms she doesn’t understand.
It is also very important to emphasise that all antidepressants take time to work, and it may be a number
of weeks before she notices an improvement. I like to support patients to follow up visits during this
period of waiting.
Furthermore, I usually point out that counselling is an important part of treating depression, and that
there may be some ways in which she can learn to help herself through this difficult illness.
I would also tell her that she would need to stay on the therapy for at least six months,
and that she should not stop it suddenly, or she may suffer from discontinuation
effects.
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Question 5
Would you prescribe any other drug therapy? If yes, what drug, dose and frequency?
I wouldn’t prescribe any other drug therapy at this stage. Later in the course of the
illness, of any initial drug therapy had failed over sufficient time (e.g 3-6 months),
then I would consider changing her to a different class of agent.
Some respondents suggested the use of benzodiazepine in this setting. Benzodiazepines can be used to
tide a patient over until the antidepressant starts to work, but the possibility of addiction and of
withdrawal agitation needs to be balanced against the short-term benefit.
Question 6
For how long after initial response would you expect to maintain antidepressant
therapy?
In my view, antidepressant therapy needs to be regarded as long term. I would not
consider cutting down on the maintenance dose in under 3 months, and normally
expect patients to stay on this therapy for at least six months. Some patients may need
to stay on antidepressants longer than this.
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