Enhanced Service standards require the use of screening procedures and note that recognition of depression improves outcome even when the patient does not comply with treatment.

Early detection and treatment of depression seems to decrease the duration of the illness.

Direct presentation of depression is difficult for patients.

As many as 40-60% of depressed people volunteer physical symptoms to their GP, rather than psychological symptoms. This may be because they do not recognise their symptoms as psychological or because of fears about stigma. Screening instruments make it easier for them to discuss their experiences and concerns.

Studies show a marked variation in the ability of general practitioners to make the diagnosis. One study showed that about half the patients presenting with depression are not recognised at presentation. What is more, only a further 10% are subsequently recognised and 20% remit in this time. The remaining remained unrecognised even after 6 months. Another study found that general practitioners detected depression in only 36% of patients scoring highly in the General Health Questionnaire. Screening instruments can improve detection.

When to use – Based on national survey figures on adults aged 16-64 years of age we can expect 1600 women and 1100 men in the Highlands to suffer from a depressive illness in any one week. A further 6000 women and 3700 men to have mixed symptoms of anxiety and depression in a particular week.

Features that are characteristics of “accurate GP diagnosis” are:

Appearing not to be hurried
Being good listeners
Using relevant questions
Showing genuine concern
Pick-up on verbal and non-verbal cues

It is important to be extra vigilant for depression in the following high risk groups: -

Those with: -

Ø A previous history of depression

Ø A family history of depression

Ø Recent bereavement (or anniversary of bereavement)

Ø Multiple adverse life events

Ø Chronic physical illness

Ø Frequent attendance at surgery

The Two Question Test

The simplest screen for depression is the Two Question Test.

During the last month, have you often been bothered by feeling down, depressed or hopeless?
During the last month, have you often been bothered by little interest or pleasure in doing things.

If the patient answers yes to these questions further assessment for diagnosis is indicated. The PHQ questionnaire would be an appropriate way to confirm the diagnosis objectively.

DIAGNOSIS

Diagnostic criteria

The ICD – 10 criteria for depression are

Diagnosis of moderate/severe depression may be made when a patient describes

LOW OR SAD MOOD

LOSS OF INTEREST OR PLEASURE

REDUCED ENERGY

Associated symptoms are frequently present

• Disturbed sleep (Insomnia/ hypersomnia)

• Worthlessness or guilt

• Reduced concentration

• Disturbed appetite (loss or increase of appetite/weight)

• Suicidal thoughts or acts

• Retardation or agitation

• Symptoms of anxiety or nervousness

• Reduced self esteem or self confidence

• Bleak or pessimistic views of the future

Use of written questionnaires

If written questionnaires are to be used in aiding diagnosis they must be completed in the surgery to be valid.

Most questionnaires are copyright to publishing companies or authors, even if they are published on the web or in text books. If you choose to use any questionnaire be sure that you are buying authorised copies or that your material is free from legal entanglements.

For this reason we recommend the use Of the PHQ-9 as permission has been granted by Pfizer for its use in association with these guidelines.

The Patient Health Questionnaire (PHQ-9)

The Patient Health Questionnaire contains a brief, 9-item, patient self-report depression assessment specifically developed for use in primary care (PHQ-9). The PHQ-9 has demonstrated usefulness as an assessment tool for the diagnosis of depression in primary care with acceptable reliability, validity, sensitivity, and specificity. The nine items of the PHQ-9 come directly from nine DSM-IV signs and symptoms of major depression.

Patients should not be diagnosed solely on the basis of a PHQ-9 score.

The clinician should corroborate the score with clinical determination that a significant depressive syndrome is present. After making a provisional diagnosis with the PHQ-9, there may be additional psycho-social considerations that may affect decisions about management and treatment.

In addition to its use as a diagnostic instrument, the PHQ-9 can also be used as a depression severity tool for monitoring treatment.

PATIENT HEALTH QUESTIONNAIRE – PHQ – 9

Patient Name:________________________ Date:___________________________

Over the last 2 weeks, how often have you been bothered by any of the following problems?

	Not at all	Several days	More than half the days	Nearly every day
Score:	0	1	2	3
a. Little interest or pleasure in doing things
b. Feeling down, depressed, or hopeless
c. Trouble falling/staying asleep, sleeping to much
d. Feeling tired or having little energy
e. Poor appetite or overeating
f. Feeling bad about yourself – or that you are a failure or have let yourself or your family down
g. Trouble concentrating on things, such as reading the newspaper or watching television
h. Moving or speaking so slowly that other people could have noticed. Or the opposite – being so fidgety or restless that you have been moving around a lot more than usual
i. Thoughts that you would be better off dead or of hurting yourself in some way

If you checked off any problem on this questionnaire so far, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?

Not difficult at all Somewhat Difficult Very Difficult Extremely Difficult

Total Number of Symptoms:____________________ Total Score: ____________________

Reproduced with the permission of Pfizer Limited
Using PHQ-9 for Diagnostic Assessment

Of the 9 items in question 1, include only those that are checked at least “More than half the days”, except count the suicide item if present “at all”.

At least one of item 1a or item 1b must be endorsed as more than half the days for a depression diagnosis. Also question 2 for functional impairment must be answered at least “Somewhat difficult”.

Using PHQ-9 for Severity of Depression Measure

Of the 9 items in question 1, using the score for each answer, sum the total for a severity score.

DIAGNOSTIC CATEGORIES FOR DEPRESSION

PHQ-9 Symptoms & Impairment	PHQ-9 Severity	Provisional Diagnosis	Treatment Recommendations**
1 to 4 symptoms, functional impairment	< 10	<Mild or Minimal Depressive Symptoms	Reassurance and/or supportive counselling Education to call if deteriorates
2 to 4 symptoms, question a or b +, functional impairment	10-14	Moderate Depressive Symptoms (Minor Depression)*	Watchful waiting Supportive counselling If no improvement after one or more months, consider use of antidepressants or brief psychological counselling
=/> 5 symptoms, questions a or b +, functional impairment	15-19	Moderately Severe Major Depression	Patient preference for antidepressant and/or psychological counselling
=/> 5 symptoms, question a or b +, functional impairment	>20	Severe Major Depression	Antidepressants alone or in combination with psychological counselling

· *If symptoms present for >2years, Chronic Depression, or functional impairment is severe, remission with watchful waiting is unlikely, immediate active treatment indicated for moderate depressive symptoms (minor depression)

· **Referral or co-management with mental health specialty clinician if patient is high risk suicide risk or has bipolar disorder, an inadequate treatment response, or complex psychosocial needs and/or other active mental disorders.

Reproduced with the permission of Pfizer Limited

Any indication of suicide or self-harm should be followed by more detailed risk assessment.

Treatment

Treatment recommendations differ between mild, moderate and severe depression

Mild depression is defined by presence of two of the triad of low mood, loss of interest and reduced energy and two other symptoms over at least two weeks. (PHQ scores of 10- 14)

Moderate depression is defined by three to four features in addition to low mood, loss of interest and reduced energy, occurring for at least two weeks. (PHQ scores of 15-19)

Severe depression is usually marked by agitation or retardation and the patient may be reluctant or unable to describe other features in detail. Both social functioning and work performance are likely to be disrupted. (PHQ scores of > 20)

Mild depression should be treated by education and watchful waiting. Non-drug strategies are to be preferred to drug treatment.

Watchful Waiting

In mild depression a period of watchful waiting is recommended. Regular appointments at two weekly intervals with the same GP will allow for progress or deterioration to be monitored. PHQ-9 can be readministered.

Psychosocial Support and Education

GPs should be confident of the proven efficacy of GP support and counselling and be positive about the benefits of giving time to depressed patients.

The high proportion of patients presenting with somatic symptoms means that often GPs will spend time excluding physical conditions, thereby gaining the patient’s trust and increasing understanding of their depression.

Patients may benefit from information on the nature of depression. Discussion between doctor and patient can help ensure a shared view of the illness. Talking to patients in terms of depression altering their thinking, feelings and behaviour as well as having physical effects can help clarify the nature of their difficulties (see Williams, 2001).

Patient education leaflets can be found at www.prodigy.nhs.uk/PILs .

Listening is essential since often the problems cannot be solved, but talking about them may bring relief. It may be useful for people to have access to a confidential help line outside of surgery hours. Breathing Space provides such a service.

In depression people often overlook potential solutions to life difficulties. Simple problem solving techniques can often be used to support the patient. This involves the patient in their own management and encourages them to set an agenda determined by their own priorities.

Self help web sites for people with mild depression/depressive symptoms can be found at www.livinglifetothefull.com

www.moodgym.anu.edu.au

Reduced activity rates often result in people losing sources of pleasure and social contact. Discussion of ways to re introduce such stimulation can be helpful, as can ideas on reorganising work commitments and obligations in order to adjust to lowered capacity for decision making and activity.

Exercise has been shown to be beneficial for low mood. GPs can discuss exercise with patients and encourage them to take up a regular programme suited to their needs.

Unhelpful behaviours, such as drinking too much or excessive spending, may develop in an attempt to alter mood. A check for the presence of such maladaptive self “help” strategies may help prevent their escalation and reduce secondary life difficulties developing.

Poor sleep can compound depression and difficulty in coping. Sleep hygiene should be checked and advice on good sleep habits be given.

A useful patient leaflet “Insomnia (Poor Sleep)” is available On-line at: - http://www.prodigy.nhs.uk/PILs/

Other strategies

Counselling is not specifically a treatment for depressive illness, although it may have particular benefits in helping patients deal with social stresses, interpersonal difficulties and family problems which may have preceded the depression or developed during the depressive episode.

Other forms of psychological intervention such as anxiety management, relaxation training, stress management, assertiveness training are not contra-indicated and may be helpful for certain individuals.

These strategies are not a substitute for active treatment but they can be useful adjunct to it. Fact sheets giving details of local self help resources, telephone help lines etc; should be available in surgeries.

Moderate depression should be treated by anti-depressant medication and/or cognitive behavioural therapy. The latter might be provided through self help materials in the first instance.

Computerised/Book Based self help is available as for mild depression.

It may be useful for people to have access to a confidential help line outside of surgery hours. Breathing Space and Samaritans provides such a service.

Handouts for self help for depression are published in Overcoming Depression: A Five Areas Approach by Chris Williams, www.arnoldpublishers.com ,and linked training materials on www.calipso.co.uk

See later section for referral to Cognitive Behavioural Therapists

Severe depression requires anti-depressant medication and consideration of Referral to Mental Health Specialists. Risk assessment is essential.

Reviewing Progress

Patients are more likely to implement advice if they know the GP will see them again soon to check whether the advice has been implemented or was helpful.

Contact at fortnightly intervals for moderate depression and initially weekly in severe depression should be considered, with contact remaining at 2-3 months intervals throughout treatment.

Referral to Mental Health Specialists

Psychiatry

Psychiatrists are happy and willing to see all patients with depression or any other psychiatric disorder if the general practitioner feels this necessary and outlines the reasons for requesting a psychiatric opinion in the referral letter. Guidelines for consideration as to what and when to refer include:

Severe depression often with psychotic ideation where admission to hospital may be required

Where there is suicidal ideation and you consider the patient to be at risk

Failure to respond to treatment with at least one antidepressant drug despite adequate dosage and duration of treatment

Chronic illness where the GP wishes advice as to continued management

Where management is difficult or stressful and the GP feels in need of support or a break

Where the GP wishes advice as to referral to other areas of the service

At the patient’s request if the GP feels this is appropriate

Community Mental Health Services

The structure of the Community Mental health Services varies throughout the Highlands and therefore there are local arrangements in place for referrals. Teams may compromise of Social Workers, Occupational Therapists and Community Psychiatric Nurses. They can offer a range of core skills such as assessment, treatment and care, outcome evaluation and health education. Some teams have specialists in Cognitive Behavioural Therapy. Community Mental Health Teams will consider referrals for any patient who is or is suspected to be suffering depression.

Consider referral to Community Mental Health if the patient:

Ø Is aged 16 or over and has left school

Ø Is isolated and vulnerable

Ø Has a previous history of mental health problems

Ø Has thoughts of self harm and/or feelings of hopelessness

Ø Abnormal grief reaction

Ø Presents with multiple psychosocial problems

Ø Has a history of poor coping skills

Referral to Cognitive Behaviour Therapists

CBT is particularly suitable for those who

Can not or do not wish to take drugs
Are frequent relapsers
Are depressed about being depressed
Experience hopelessness and feelings of helplessness
Have chronic low self-esteem
Complain of negative thoughts

Development plans for Psychological Therapies across Highlands include the establishment of Cognitive Behaviour Therapists posts for each area. These should be coming on stream during the lifetime of these Guidelines.

Referral to Psychology

Psychologists accept referrals of patients with all forms of depressive difficulties for assessment and treatment. Psychological therapy may be particularly relevant when one or more of the following apply:

1. Duration of six months in spite of adequate drug therapy

2. Refusal to use antidepressants/failure to respond to medication/other factors preventing drug treatment

3. History of relapses/recurrent episodes

4. Concurrent/alternative diagnosis or difficultly, particularly anxiety disorders, self injury

5. Depression is part of a pattern of difficulties arising out of adverse or traumatic early life experiences

In order for patients to see a psychologist they need to be able to attend a clinic during working hours.

MOOD GYM

MoodGYM is a free, interactive internet-based program designed to prevent and decrease symptoms of depression.

MoodGYM aims to teach you how you can feel less stressed, depressed and anxious, and better able to cope with your life.

From MoodGYM we hope you will learn helpful ways of thinking about problems, how to improve your self-esteem, and how best to relate to others (and to be more assertive). You will also learn how to increase the pleasure in your life, how to relax and how to cope with a relationship break-up.

MoodGYM consists of a number of interactive modules. These should be completed in order, as each module builds upon material covered in earlier modules. As you move through the program, you will be presented with information, animated demonstrations, quizzes and ‘homework’ exercises.

Your answers to the exercises are recorded in your own personal MoodGYM Workbook.

The Workbook is important as it helps you track your progress as you move through the modules.

Think of MoodGYM as an interactive self-help book. There are many books about how to improve your mental health.

The advantage of MoodGYM is that it can give you feedback about your mental health, and you can use the online exercise to work out how to handle life’s challenges better.

Moodgym is located at http://moodgym.anu.edu.au

Living Life to the Full

Living Life to The Full On-line is a new life skills resource. The course has been written by a psychiatrist who has many years of experience using a Cognitive behaviour therapy (CBT) approach and also in helping people use these skills in everyday life. During the development phase of the course, a wide range of health care practitioners and members of the public have used each module. Joining and using the site is entirely free.

The Living Life to The Full modules have been devised to help people develop key life skills to help them tackle common problems we all face from time to time in life.

The modules act as a free and stand-alone resources to be worked through at home in the person's own time. They may sometimes be supported by sessions with a health care practitioner. The materials use modern educational techniques and the evidence-based cognitive behaviour therapy (CBT) approach to help bring about helpful change.

Living Life to The Full On-Line can be found at: - http://www.livinglifetothefull.com/elearning/

Breathing Space

Breathing Space is a free, confidential phone line you can call when you’re feeling down. You might be worried about something – money, work, relationships, and exams – or maybe you’re just feeling fed up and can’t put your finger on why.

Sharing your feelings with your friends or talking with your family can be difficult – pretending everything is okay seems by far the easiest way to deal with things. Maybe you’re afraid to let down your guard and tell those close to you what’s really on your mind – you don’t want to worry them, or perhaps you just don’t know how to explain the way you are feeling.

That’s when you might want to talk to the people at Breathing Space. They’re available to listen to you when you’re feeling low. They can offer advice, or suggest people who can help you with more specific problems.

There are people at Breathing Space to listen to you every night from 6pm-2am, when you’re wide awake and running over problems in your mind.

The service is completely confidential and it’s a free phone number – 0800 83 85 87 (Minicom: 0800 31 71 60) – so it won’t show up in your phone bilss*.

So the next time you’re feeling down, it might help to get some Breathing Space.

*If you’re calling from a mobile, check out what you have with them – they might charge you for your call.

http://www.breathingspacescotland.co.uk

Samaritans'

Samaritans is available 24 hours a day to provide confidential emotional support for people who are experiencing feelings of distress or despair, including those which may lead to suicide.
In the UK dial 08457 90 90 90, for the cost of a local call.

http://www.samaritans.org

Anti depressant Swapping

Antidepressants in Pregnancy and Breast-feeding

St John’s Wort

Patients with low mood or loss of interest plus at least four of the other diagnostic features mentioned are most likely to respond to drug treatment. For these patients with moderate to severe depression, antidepressants should be considered the mainstay of treatment.

Antidepressants are effective in the treatment of moderate to severe depression. However, antidepressants do not appear more efficacious than placebo in milder depression and are not recommended for the initial treatment of mild depression. In milder depressive states non-drug strategies are often preferable to drug treatment.

The fact that a patient’s depression is “understandable” should not deter the GP from prescribing antidepressants since they are just as likely to be effective. 70% of patients are likely to respond to the first intervention offered.

Antidepressant Treatment – Which Drug to Use

All antidepressants have broadly similar efficacy (Song et al 1993) and therefore the choice of drug for a particular patient will depend on the nature of the symptoms, side-effect profile, concomitant therapy, concurrent illness, patient preference and safety in over-dose. Previous response to treatment is also a strong indication to repeat that treatment in future episodes.

The antidepressant whose profile best fits the ideal for an individual patient should be prescribed. In the absence of special factors, choose antidepressants which are better tolerated, safer in overdose, and more likely to be prescribed at effective doses. Since there is most evidence for SSRIs, they should be regarded as the preferred option for first line use.

When prescribing an SSRI, fluoxetine is a reasonable choice as it has efficacy similar to other SSRIs, but is available as a generic, and hence provides additional benefit in terms of cost effectiveness.

When considering toxicity in overdose, the evidence to date suggests that SSRIs, newer tricyclics, mirtazapine and reboxetine are safer than older tricyclics or venlafaxine.

The newer agents may have a place in treatment of patients for whom first choice drugs are poorly tolerated or ineffective.

Cost Effectiveness

The cost of these drugs should also be taken into account when a decision is made to prescribe, especially when choosing between drugs in the same class.

Antidepressants account for a large proportion of the primary care drugs spend.

TCAs are by far the cheapest agents, especially compared to newer antidepressants, but they carry the risk that they may be prescribed in sub-therapeutic doses, e.g. to avoid adverse effects which are common with TCAs. Generic SSRI preparations such as fluoxetine offer a safer but relatively inexpensive alternative.

The Elderly

The same principals apply to the elderly as the adult population in the decision on which antidepressant to use. Concomitant therapy and concurrent illness are likely to be of greater relevance.

The main differences in the elderly regarding the use of antidepressant drugs relate to altered distribution, metabolism and excretion and their increased sensitivity to the effects of these drugs. This provides the reasoning behind the adage “start low and go slow” with antidepressant doses in this population. Psychomotor impairment and postural hypotension are particularly problematic in the elderly and there is therefore an argument for generally avoiding the older tricyclics (Lasser et al 1998).

Starting Treatment

SSRIs can usually be started at a therapeutic dose.

TCAs should be gradually increased to the therapeutic dose over 1-2 weeks, or as quickly as can be tolerated.

Patients should be advised of the likely early side effects, and the lag time before symptoms noticeably improve.

Increased anxiety/agitation can be problematic at the early stages of treatment with an SSRI. Judicious short-term use of a benzodiazepine may be helpful in such situations.

CSM Advice Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in the differential diagnosis of all patients who develop drowsiness, confusion or convulsion while taking an antidepressant.

Compliance Issues

Compliance with prescribed medication for all chronic conditions is estimated at 50%. There are a variety of reasons why patients cannot or will not comply with their prescribed medication, but there are particular reasons why compliance may be a problem with antidepressants.

Lack of initial benefit
High incidence of side effects, particularly occurring prior to the onset of antidepressant action
Reluctance to accept the diagnosis of depression
Fear that antidepressant medication is addictive
Symptom improvement leading to patient stopping drugs, with subsequent relapse
Difficulty obtaining relevant information

Before starting treatment compliance can be improved by

Give positive advice regarding the benefits of treatment
Reinforce that antidepressant are not addictive
Inform patients about potential side effects
Reinforce the importance of not discontinuing treatment before or during the continuation treatment phase
Inform the patient about the possibility of discontinuation symptoms on missing doses, or stopping antidepressant medication
Reassure regarding the low risk of discontinuation problems if reduced and stopped under supervision
Advise on the timing of dosage
That improvement may not be noticed until the patient has been on the medication for a week or more
Advice that treatment is likely to be continued for at least 6 months from time of improvement

Community Pharmacists are usually pleased to offer advice to patients on antidepressants.

Drug Group	Description	Suggested Drug
Serotonin Selective Reuptake Inhibitors	Recommended for first line use, especially in older or physically ill patients, more susceptible to side effects. They are better tolerated than TCAs and are more likely to be prescribed at adequate doses for an adequate period. (Rosholm et al 1997). Fewer anticholinergic and cardiovascular side effects than TCAs. Are not without side effects. These are mainly gastrointestinal e.g. nausea, diarrhoea.	Fluoxetine
Tricyclic Antidepressants (TCA)	Use at adequate dosage often limited by side effects. Anticholinergic side effects e.g. constipation, blurred vision and dry mouth are common. Cardiovascular effects such as arrhythmias and hypotension can also occur. TCAs can prolong the QT interval. Sedation can be problematic but may also be useful in some patients. Tolerance to some side effects can develop but may necessitate gradual dosage increases. Amitriptyline is comparable in efficacy and safety to other TCAs but is recommended, as it is more cost effective.	Amitriptyline
Serotonin Norepinephrine Reuptake Inhibitor (SNRI)	Not for first line use. NICE recommend initiation and monitoring under specialist supervision only. May have greater efficacy than SSRIs at doses of 150mg or greater. Dose responsive so can titrate dose for further effect. Side effect profile similar to SSRIs but can lower/elevate blood pressure. Note requirement for pre-treatment ECG and B.P. check.	Venlafaxine
Norepinephrine and Serotonin Specific Antidepressants (NASSA)	Not for first line use. Weight gain can be a problem. Low incidence of sexual dysfunction. May potentiate other centrally acting sedatives. Suitable for patients who require sedation but for whom a TCA is not suitable.	Mirtazepine
Norepinephrine Reuptake Inhibitor (NARI)	Normally used after consultation with secondary care. Is not sedating but insomnia can be a problem, along with some anticholinergic side effects.
Monoamine Oxidase Inhibitor (MAOI)	Normally used after consultation with secondary care.	Phenelzine

Recommended Dosage

Normal recommended dose range for the ten most frequently prescribed antidepressants in Highland in 2002-3 are shown below. Please see NHS Highland Joint Formulary for currently recommended antidepressants.

SSRIs

Fluoxetine

Citalopram

Paroxetine

Sertraline

NEWER ANTIDEPRESSANTS

Venlafaxine**

Mirtazapine

OLDER TCAs

Amitriptyline

Clomiprammine

Dosulepin

NEWER TCAs

Trazodone

ADULTS

20mg

20-60mg

20-50mg*

100-200mg

75-375mg

15-45mg

150-200mg

150-225mg

200-300mg

ELDERLY

20mg

20-40mg

50-200mg

75-375mg

15-45mg

Not Recommended

150-300mg

*Note CSM 2004 advice. Recommended dose for depression is 20mg

**Applies only to the immediate release preparation

Failure to respond despite good compliance

Adult

• No response after 4 weeks

• Partial response after 4 weeks, continue for a further 2 weeks. Partial response converted to full response at 6 weeks?

Elderly

• No response after 6 weeks

• Partial response after 6 weeks, continue for a further 3 weeks. Partial response converted to full response at 9 weeks?

If a full response is not obtained within the time scales outlined above then:

• First increase the dose of the current antidepressant to the upper limit of the therapeutic range, provided the patient can tolerate any side effects.

• Switch to a drug of a different class. Different classes of antidepressant in addition to

MAOIs, TCAs and SSRIs include SNRI, NARI, and NaSSAs. Call Pharmacy Department at

New Craigs Hospital for advice if required (Tel: 01463 704663).

• Washout periods are required for switching between certain antidepressants (see below)

Antidepressant Swapping – General Guidelines

1. Fluoxetine, due to its long plasma half-life and active metabolite, may be stopped abruptly if the dose is 20mg/day.

2. When swapping from one antidepressant to another, abrupt withdrawal should usually be avoided. Cross tapering is preferred, where the dose of the ineffective or poorly tolerated drug is slowly reduced while the new drug is slowly introduced.

3. The speed of cross tapering is best judged by monitoring patient tolerability. No clear guidelines are available, so caution is required.

4. Note that the co-administration of some antidepressants is absolutely contra-indicated. See BNF Chapter 4.3.2 and Appendix 1. In other cases, theoretical risks or lack of experience preclude recommending cross tapering.

5. Withdrawal ideally involves a gradual reduction to a low dose of antidepressant before stopping.

6. Potential dangers of simultaneously administering two antidepressants include pharmacodynamic interactions (serotonin syndrome, hypotension and drowsiness) and pharmacokinetic interactions (e.g. elevation of tricyclic plasma levels by some SSRIs).

Serotonin Syndrome – Symptoms

Restlessness

Sweating

Tremor

Shivering

Myoclonus

Confusion

Convulsions

Death

Duration of Treatment

Inadequate or no treatment for six months after the illness has resolved can result in relapse rates as high as 50%.

Continue antidepressant drug treatment for a minimum of 6 months after remission of symptoms in adults, and for a minimum of 12 months in the elderly.

Continue the same dose of antidepressant used that produced a response to treatment.

Patients with residual depressive symptoms and other factors increasing risk of relapse should continue treatment for longer with the duration taking into account the persistence of these factors.

Maintenance Therapy

The risk of recurrence of depressive illness is high and increases with each episode.

Maintenance therapy should be at the same dose of antidepressant that produced a response to treatment.

The decision to go on to maintenance therapy, rather than stop treatment at the end of the continuation phase, must be made on clinical grounds in discussion with the patient. Maintenance treatment with antidepressants is indicated for patients with:

3 or more episodes of depression in the last 5 years.
More than 5 episodes altogether.
Fewer recurrent depressive episodes but with persistent risk factors for relapse/recurrence

Re-evaluate patients on maintenance treatment, taking into account age, co morbid conditions and other risk factors in the decision to continue the treatment beyond 2 years.

For the elderly, with two or more relapses, life long therapy is indicated.

Discontinuation

Discontinuation symptoms can occur with all the major classes of antidepressant

Symptoms start abruptly within a few days of stopping the antidepressant

Symptoms usually resolve with days to 3 weeks

Risk factors: longer duration of treatment, short half life drugs such as paroxetine and venlafaxine

If administered for 8 weeks or more, antidepressants should be reduced gradually over a minimum of 4 weeks. Fluoxetine may be an exception to this rule. Rapid discontinuation may be required for severe adverse reactions or if the patient switches into a manic state

Ideally taper the dose over 6 months in patients who have been on longer-term maintenance treatment

If discontinuation symptoms are mild then explanation and reassurance are often all that is required

If severe symptoms are experienced consider the re-introduction of the original antidepressant (or another from the same class with a longer half life e.g. fluoxetine for paroxetine) and reduce gradually.

Discontinuation symptoms are varied and differ depending on the class of antidepressant. Symptoms common to all classes include gastro-intestinal disturbance (nausea, abdominal pain, diarrhoea), general somatic distress (sweating, lethargy, and headache), sleep disturbance (insomnia, vivid dreams, nightmares) and affective symptoms (low mood, anxiety, irritability). With the SNRI/SSRIs the commonest symptoms appear to be dizziness and sensory abnormalities such as numbness or electric shock like sensations. Discontinuation symptoms may be a useful clue to convert non-compliance.

Antidepressants in pregnancy and breast-feeding

Updated advice in these areas can be obtained locally from the Area Medicines Information Service (Tel. 01463 704288) or New Craigs Pharmacy Department (01463 704663).

Carefully consider the benefit/risk ratio of prescribing antidepressants during pregnancy and breastfeeding for both mother and baby/foetus. Taking into account:

a. Antidepressants are not licensed for use in pregnancy & breastfeeding.

b. There should be a clear indication for drug treatment

c. Lowest effective dose should be given for the shortest period necessary

d. Drugs with a better evidence base (generally more established drugs) are preferable.

Antidepressants in the first trimester

Evidence indicates no increased risk of major malformation or spontaneous abortion following exposure to TCAs or SSRIs in early pregnancy. There is most evidence for amitriptyline and imipramine in the TCA class, and most evidence for Fluoxetine in the SSRI class.

· Carefully assess the risks of stopping TCAs or SSRIs in relation to the mother’s mental state & previous history

· There is no indication to stop TCAs or SSRIs as a matter of routine in early pregnancy

· If a woman becomes depressed during pregnancy, antidepressants should be prescribed with caution and specialist advice sought

Antidepressants after the first trimester

In later pregnancy there is evidence of neonatal toxicity and withdrawal at birth in infants exposed to antidepressants. There are also concerns about the possible effects on infant neurodevelopment.

· Neonates exposed to antidepressants during pregnancy should be monitored for withdrawal following delivery

· Consider dose reduction and/or discontinuation 2 to 4 weeks before expected delivery date then recommence after delivery.

Antidepressants during breast-feeding

Manufactures advise avoiding antidepressants during breast-feeding due to their excretion in breastmilk and the evidence base is very limited. However there is no clinical indication for women treated with TCAs (except doxepin) or the SSRIs paroxetine, sertraline or fluoxetine to stop breast-feeding provided the infant is healthy and progress is monitored.

· Breast-feeding should take place immediately prior to taking medication, ideally as a single daily dose just before the infant’s longest sleep period

· Ideally avoid breast feeding when maternal plasma levels are highest, usually 1 to 2 hours after taking the medication

· Paroxetine or Sertaline may be the preferred SSRIs.

A patient information leaflet concerning antidepressants and breastfeeding has been produced by NHS Highland. This is written in plain English and is designed to assist the GP in enabling the patient to come to an informed decision.

Antidepressants in cardiovascular disease

When initiating treatment in patient with ischaemic heart disease, sertraline is the treatment of choice.

ST JOHN’S WORT

When a patient has declined a number of offers of treatment for depression or expressed a preference for St John’s Wort they should be informed that St John’s Wort may be of benefit in mild and moderate depression. They should also be informed, as should those taking St John’s Wort, of the interactions of St John’s Wort with other drugs, of the lack of information on longer term efficacy and side effects and of the different strengths of the preparation available and the uncertainty that arises from this

Always check if a patient is taking St John’s Wort if considering prescribing an antidepressant.

Suicide Screening Questions

When a diagnosis of Depression is made, suicide risk requires assessment. For all depressed patients the following questions may be asked:

· Have these symptoms/feelings we've been talking about led you to think you might be better off dead?

· This past week, have you had any thoughts that life is not worth living or that you'd be better off dead?

· What about thoughts about hurting or even killing yourself? If YES, what have you thought about?

Have you actually done anything to hurt yourself?

Risk Factors

Previous attempt
Older age
Living alone/no social support
Substance misuse/ alcohol,
Chronic disease
Helplessness

ASSESSMENT OF SUICIDE RISK

Risk	Description	Action
Low Risk	No current thoughts, no major risk factors * See risk factors above	Continue follow-up visits and monitoring
Intermediate Risk	Current thoughts, but no plans, with or without risk factors	Assess suicide risk carefully at each visit and contract with patient to call you if suicide thoughts become more prominent; consult with an expert as needed.
High Risk	Current thoughts with plans	Emergency assessment by qualified expert

TO FROM	*Tricyclics*	*Citalopram*	*Fluoxetine*	*Paroxetine*	*Sertraline*	*Trazodone/* *nefazodone*	*Venlafaxine*	*Mirtazapine*	*Reboxetine*
Tricyclics	Cross taper cautiously	Halve dose and add citalopram then slow withdrawal. **	Halve dose and add fluoxetine then slow withdrawal. **	Halve dose and add paroxetine then slow withdrawal. **	Halve dose and add sertraline then slow withdrawal. **	Halve dose and add trazodone/ nefazodone then slow withdrawal. **	Cross taper cautiously starting with venlafaxine 37.5mg at night	Withdraw before starting mirtazapine cautiously	Cross taper cautiously
Citalopram	Cross taper cautiously. **	-	Withdraw then start fluoxetine.	Withdraw and start paroxetine at 10mg/day	Withdraw and start sertraline at 25mg/day	Withdraw before starting titration of trazodone/ nefazodone	Withdraw. Start venlafaxine 37.5mg/day. Increase very slowly	Withdraw before starting mirtazipine cautiously	Cross taper cautiously
Paroxetine	Cross taper cautiously with low dose of tricyclic.**	Withdraw and start citalopram	Withdraw then start fluoxetine	-	Withdraw and start sertraline at 25mg/day	Withdraw before starting titration of trazodone/ nefazodone	Withdraw paroxetine. Start venlafaxine 37.5mg/day and increase very slowly	Withdraw before starting mirtazipine cautiously	Cross taper cautiously
Fluoxetine1*	Stop fluoxetine. Start tricyclic at very low dose and increase very slowly	Stop fluoxetine. Wait 4-7 days. Start citalopram at 10mg/day and increase slowly	-	Withdraw fluoxetine. Wait 4-7 days, then start paroxetine 10mg/day	Stop fluoxetine. Wait 4-7 days. Start sertraline at 25mg/day	Stop fluoxetine. Wait 4-7 days. Start low dose trazodone/ nefazodone	Withdraw. Wait 4-7 days. Start Venlafaxine at 37.5mg/day. Increase very slowly.	Withdraw. Wait 4-7 days before starting mirtazapine cautiously	Withdraw. Start reboxetine at 2mg bd and increase cautiously
Sertraline	Cross taper cautiously with very low dose of tricyclic. **	Withdraw then start citalopram	Withdraw then start fluoxetine	Withdraw then start paroxetine	-	Withdraw before starting trazodone/ nefazodone	Withdraw. Start venlafaxine at 37.5mg/day	Withdraw before starting mirtazapine cautiously	Cross taper cautiously
Trazodone/ nefazodone	Cross taper cautiously with very low dose of tricyclic.	Withdraw then start citalopram	Withdraw then start fluoxetine	Withdraw then start paroxetine	Withdraw then start sertraline	-	Withdraw. Start venlafaxine at 37.5mg/day	Withdraw before starting mirtazapine cautiously	Withdraw, start reboxetine at 2mg BD and increase cautiously
Venlafaxine	Cross taper cautiously with very low dose of tricyclic. **	Cross taper cautiously. Start with 10mg/day	Cross taper cautiously. Start with 20mg every other day	Cross taper cautiously. Start with 10mg/day	Cross taper cautiously. Start with 25mg/day	Cross taper cautiously	-	Withdraw before starting mirtazapine cautiously	Cross taper cautiously
Mirtazapine	Withdraw then start tricyclic	Withdraw then start citalopram	Withdraw then start fluoxetine	Withdraw then start paroxetine	Withdraw then start sertraline	Withdraw then start trazodone/ nefazodone	Withdraw then start venlafaxine	-	Withdraw then start reboxetine
Reboxetine	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	Cross taper cautiously	-