Medication use in depression

Indications for the use of antidepressants are discussed in “Treatment” section above. When confronted with the wide range of available antidepressants, remember that despite marketing claims to the contrary: ™ All antidepressants are equally effective for most depressions at a group level (though note that there is some evidence to support use of TCA, SNRI, NASSA in melancholia) ™ All antidepressants take equally long to be effective (usually 2-6 weeks) ™ It’s best to be familiar with the use of a small number of antidepressants When initiating antidepressants it is important to persist to allow an adequate trial.
Three factors make up an adequate trial
™ Dose: An average level for that agent, as recommended by the PI.
™ Duration: Three weeks to six weeks
™ Compliance: Confidence that the patient is compliant
Choice of antidepressants
Past response
The best predictor of future response is past response. Previous response to a particular
antidepressant overrides most other considerations.
If a patient has not previously had antidepressants, a family history of response to a
particular antidepressant (eg in a parent or sibling) may guide choice. It may indicate a
greater biological responsiveness to that agent, as well as providing a foundation of
greater patient confidence.
Side effect profile
The second consideration in medication choice is side effect profile. Although newer
agents are well tolerated overall, many individuals experience significant side effects.
For those on other medications, the risk of interactions or cumulative side effects should
be minimised. Where continued role functioning and alertness is critical (eg some
occupations, roles, parenting) sedating side effects are best avoided. Medications with
sexual side effects are best avoided in those with a biological or psychological sensitivity
to sexual difficulties.
Symptom profile
Certain patterns of depressive symptoms may respond to particular antidepressants. Evidence for this is limited, and at times these may be based on convention and analogies with older medications rather than on systematic trials. Past response and side effect profile are more powerful factors, and most antidepressants will be effective for a wide range of presentations. These are summarised in the table which follows: Do benzodiazepines have a role?
As in other conditions, benzodiazepines should be used sparingly and for brief periods.
They have potential for dependence and abuse. It is also possible that their use may
limit new learning and slow the effectiveness of psychological treatments.
They should never be used alone for treatment of depression. Their anxiolytic effects
may mask some depressive symptoms, but the depression will not resolve.
The main indication for benzodiazepine use in depression is for initial control of
insomnia. Most non-sedating antidepressants will improve the insomnia associated with
depression, but this response may take several weeks. If insomnia is present but a non-
sedating antidepressant such as an SSRI is preferred (eg due to past response), a
hypnotic such as Temazepam (Normison) 10-20mg nocte or Nitrazepam (Mogadon) 5-
10mg nocte may be useful in the initial weeks of treatment.
Anxiety symptoms associated with depression should not usually be treated with
a benzodiazepine. CBT is the treatment of choice for these symptoms. Most
antidepressants are effective in reducing anxiety.

Other medications
A number of other medications are used in treating depression where additional
symptoms are present or where first-line treatment has been ineffective. Most should
usually be used after specialist consultation.
These must be used where psychotic symptoms are present. They may also be effective
in reducing severe anxiety, and boosting or augmenting other antidepressants where
there has been incomplete response. Conventional antipsychotics such as Haloperidol
(Serenace) and Chlorpromazine (Largactil) should be used cautiously due to their side
effect profile, including the risk of irreversible movement disorders. Newer agents with
more favourable side effect profiles, such as Olanzapine (Zyprexa), Quetiapine
(Seroquel) or Risperidone (Risperdal), are preferable.
Mood stabilisers
Lithium Carbonate (Lithicarb), Carbemazepine (Tegretol) and Sodium Valproate (Epilim)
are all effective mood stabilisers. They may be used to treat depression occurring in
Bipolar Affective Disorder as well as to prevent recurrence of depression or mania in that
disorder. In other depressions they may be used to augment the effect of
antidepressants where treatment has been ineffective. Newer anticonvulsants such as
Vigabantrin may have similar effects but have not yet been systematically studied.
Lamotrigine is a useful agent in bipolar depression, but needs to be introduced over 6
weeks due to risk of Stevens-Johnson Syndrome.
Other augmentation agents
In some treatment resistant depressions augmentation with other agents (eg Thyroid Hormone) has been effective in some patients. Such augmentation should only be initiated after specialist consultation. Patient information and education
Steps for improving compliance
treatment depends on much more than pharmacology. Good initiation and compliance. In depression, apprehension and concentration and information processing ability may be impaired. Successful treatment may require
persistence for several weeks before signs of improvement are seen, and side effects
may be maximal in the first weeks of treatment, peaking before signs of improvement.
Steps which can be taken to improve compliance with antidepressants include:
Explanation and rationale
The diagnosis of depression and reasons for antidepressant use should be explained.
Dispelling misperceptions
Antidepressants are often viewed with suspicion. Common concerns include that they
may be addictive, that they will create a false “high” and that depression will recur on
cessation. A useful analogy can be to see antidepressants as like a splint or plaster in
treating a fracture, providing stabilisation to allow internal healing processes to take
place. It can be useful to explain that antidepressants are not stimulants, and a non-
depressed person taking them will feel no benefit.
Encouraging a long-term view
Expectations of immediate benefit should be reduced. A trial of antidepressants can be
explained as a medium-term investment requiring several weeks of persistence prior to
seeing a return. Foreshadowing that 10-20% of people may require a change of
antidepressant due to side effects or non-response can prevent loss of hope later.
Explaining possible side effects
Possible side effects should be explained. Many peak in the initial weeks of treatment
and then subside. Giving the patient some forewarning and allowing them a level of
control about whether to persist with side effects or change to a different agent can be
Giving relevant support material
Even the best crafted explanation may not be remembered the next day. The use of written or audiovisual materials about diagnosis and treatment will significantly enhance compliance. They may also provide the patient with a useful device for explaining and validating their condition to family and supports. Many drug companies provide sophisticated and useful patient support materials. Where these are free of excessive promotion they are a useful adjunct to treatment. Treating the subtypes of depression
Mixed anxiety and depression
A mix of anxiety and depressive symptoms may be more common than either syndrome
on its own and is usually associated with non-melancholic depression. These illnesses
are typically chronic, with exacerbations associated with periods of increased stress.
The most effective medications are SSRIs. Venlafaxine (Efexor) and Moclobemide
(Aurorix) may also be useful. Benzodiazepines should be avoided.
Severe or melancholic depression
Although a minority of cases (5-10% of all depression) the increased risk means
identification is critical. Major risk factors include a strong family history of depression
(including bipolar disorder). It is more common in the elderly, and is associated with
cerebrovascular disease. When occurring in a young person (< 40), be alert to the
possibility of a bipolar illness.
The most effective medications are probably Venlafaxine (Efexor) or the tricyclics such
as Prothiaden. Some have argued that SSRI’s are less effective in this group. A minority
of patients will require ECT, which is highly effective in this group.
c) Post-natal depression
This occurs in 10-20% of all women in the 12 months post-partum. It is usually non-
melancholic, but a small proportion will experience psychosis. Risk factors include
previous history of depression, poor social supports, ambivalent attitude towards
pregnancy and motherhood, poor relationship with own mother, pre and perinatal
complications, primiparous women.
Always consider risk issues for both mother and baby. Choice of medication will depend
on whether mother is breastfeeding (see below).
Depression as part of a Bipolar Affective Disorder
A Major Depressive episode may form one part of a bipolar affective disorder, where
history reveals episodes of clinical or subclinical mania. Melancholic and psychotic
symptoms are more common in depressions occurring in this context
The major risk in treatment of this group is that antidepressants may precipitate a swing
into mania, or trigger “rapid cycling” with more frequent switching between states.
Antidepressants should only be used with mood stabiliser cover, and treatment of this
group should usually involve specialist consultation
Depression and substance use
The use of alcohol, in particular, complicates the presentation of depression. Alcohol dependence can lead to depression, and persons who are depressed may self-medicate with alcohol. In young persons, cannabis dependence may present with amotivation, lethargy and withdrawal, thus mimicking depression. In older persons, benzodiazepine
use may precipitate depression or complicate its treatment.

It is essential to address the issues of substance use as part of the management of
depression. This might include specific drug and alcohol counselling or a detoxification

There is evidence to suggest that antidepressants are less effective when a person is
concurrently abusing alcohol or illicit drugs. Therefore a concerted effort should be made
to encourage the person to cease or substantially reduce the amount consumed prior to
commencing an antidepressant.
Adolescents and young people
Depression is common in this age group and is generally under-recognised. It is likely to
be multifactorial, involving significant family and developmental issues, and is often
precipitated by a crisis (e.g. relationship breakup or failing exams). Drug and alcohol
problems may often be associated.
Depression may be more difficult to detect in younger people, because of greater
reluctance to seek help, greater need for sensitive interviewing and greater likelihood of
atypical depressive symptoms such as boredom, irritability and pain.
Melancholic or psychotic features are rare, but if present may indicate an evolving
Bipolar Affective Disorder. If these are present, urgent referral to specialist mental health
service should occur.
Antidepressants should rarely, if ever, be used in isolation in adolescents, but should be
combined with psychosocial interventions.
Depression in the elderly
Depression occurs commonly in the elderly. ‘Late-onset’ depression (i.e. first episode
after 50) tends to be associated with organic pathology, such as cerebrovascular
disease and degenerative brain disease. Also consider iatrogenic depression secondary
to medications (e.g. corticosteroids, antihypertensives).

Melancholic and psychotic features occur more commonly in the elderly. Typical
psychotic features in the elderly are delusions of guilt, poverty or somatic illness. These
symptoms may be vague or not disclosed. The GP should have a high index of
suspicion where there is significant agitation or slowing, where milder concerns about
money or health are expressed, where the patient is unusually difficult to reassure or
where there is a failure to respond to adequate doses of an antidepressant. It is critical
that psychotic features such as delusions or hallucinations are recognized (see
Assessment section). Psychotic depression will not respond to antidepressants alone,
and is associated with a much higher risk of morbidity and mortality.
Depression and Personality Disorder
Patients with serious personality disorder tend to have high rates of comorbid depression, which is often missed due to focussing on the ‘acting out’ elements of the personality disorder, such as intense anger and deliberate self-harm. It is essential to ask about symptoms of depression in this group. Vegetative symptoms like change in appetite, sleep and libido may be more sensitive markers than cognitive symptoms such as helplessness and hopelessness, which tend to be chronic in this group. Whilst simple, short-term psychological strategies can be useful for this group of patients, some will require more comprehensive psychological therapy. This may be an indication for referral to a specialist mental health service. Medication has been demonstrated to be useful in patients with personality disorder and comorbid depression. It is important to avoid losing hope. Focus on those aspects of the presentation, such as depression, that can be treated. Pregnancy and breastfeeding
The decision to continue or initiate medication during pregnancy requires careful thought. Most antidepressants fall into medium to low-risk categories. Therefore possible risks of treatment need to be weighed against the risk to the mother and foetus of untreated depression. Psychosocial treatments from support to specific CBT should always be the first choice. However, in patients with severe depression, melancholia or significant suicide risk, antidepressant use may be indicated. If a patient on antidepressants discovers they are pregnant, a decision to cease treatment should not be made without review of the seriousness, rate of onset and degree of risk posed by the previous depressive episode. Specialist assessment should usually be sought in these situations. Risk to Foetus of Antidepressants taken by mother:
Fluoxetine, Mianserin, Tranylcypromine, Venlafaxine Citalopram, Nefazodone, Sertraline. Paroxetine Lithium, Carbemazepine, Valproate, Clonazepam The postpartum period is the highest risk period for development of depression, and the question of prescribing during breastfeeding often arises. If in any doubt in dealing with this question you should feel welcome to make a referral for assessment and advice.


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