The following document was written by Dr Satvir Singh FRANZCP (Aust), FRCPsych (UK), MSc (Lon), MRCPsych (UK), DPM, MBBS Consultant Psychiatrist & Lead Consultant for Undergraduate Medical Education (Psychiatry) Kent & Medway NHS and Social Care Partnership Trust Canterbury, Kent in Dec 2007.
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DIAGNOSIS AND MANAGEMENT OF DEPRESSION

Introduction

Depression is a common disorder and 1:5 individuals may experience it in their lifetime. It is twice as prevalent in women as in men. Most commonly, it presents between the ages of 20 to 50 years of age, but children as well as older persons also present with mild to severe symptoms of depression. Suicide rate in depression is up to 4 times higher than any other mental health disorders, and 20-30 times higher than the suicide rate in general population.

Recognition of severe depression is quite easy but not so easy in cases of mild depression. Furthermore, it is a little difficult to differentiate between a normal emotional reaction to a given day to day-to-day life events such as social and financial difficulties as compared to a true depressive illness requiring medical attention.

Ideally, an initial thorough work-up as outlined in History Taking in Psychiatry – 1, 2 and 3 will help clinicians to recognise and diagnose almost all cases of depression. If for some reason one is unable to spend the required time with the patient during the first consultation, it is always useful to make another follow-up appointment within a few days or, if necessary, the same day so that you are able to assess and plan the management carefully than rush through and fail to recognise the main concerns of the patient.

It pays to remember that initial time spent with a patient during the first consultation is positively correlated with better outcome and overall patient compliance with the treatment and satisfaction.

A brief physical examination and essential haematological and biochemistry investigations not only give you the patient’s current base line physical health status but also exclude some common physical disorders, which may present with symptoms of depression. In older persons, always exclude the possibility of malignancy, diabetes, thyroid, liver and renal dysfunctions and related disorders. A routine PSA in all men aged 50 years or over, is good clinical practice.

Sometimes, the initial symptoms of lethargy, tiredness, inability to cope with day-to-day life stresses, lowered mood, disturbed sleep pattern and change in appetite and weight could well be due to the underlying occult physical pathology such as lung and pancreatic malignancies.

In case the patient does not respond to the standard methods of treatment for depression, it is advisable to re-evaluate thoroughly his/her physical state.

Diagnosis of Depression

Most psychiatric disorders present with psychological, physical (biological) and behavioural (social) signs and symptoms and it is always useful to recognise these as such in different categories. It also helps to understand the probable aetiological factors as well as management of the patient.

Following are the main psychological, physical and behavioural symptoms of depression:

Psychological Symptoms

• Low mood for at least in the last 14 days and represent a change from previous functioning


• Reduced/lack of interest and pleasure in almost all activities


• Feelings of worthlessness, self-blame, inappropriate guilt, burden on others, tearfulness, low self-esteem and confidence


• Difficulty in making decisions


• Feeling anxious or worried


• Reduced level of attention, concentration and memory problems


• Suicidal thoughts, such as life is not worth living and holds no future

Physical Symptoms

• Change in appetite and weight (reduced or increased)


• Disturbed sleep pattern (early, middle or late insomnia)


• Reduced energy level and physical activities


• Increased tiredness


• Decreased libido


• Agitation and restlessness


• Increased irritability and anger


• Change in menstrual cycle


• Constipation

Behavioural Symptoms

• Self-neglect


• Withdrawn and social isolation


• Inability to take care of household chores and related responsibilities


• Poor performance at work – time keeping/absences


• Dropping out from various social activities, hobbies and interests

In clinical practice, mild to moderate severity of depression would have significant number of psychological symptoms, while in severe depression, there will be a lot more physical symptoms plus depressive delusions such as delusions of sin, poverty, malignancy & infection and other irrational fears and wrong-doings in life (overvalued ideation).

As per ICD-10, the following criteria are applied to differentiate between mild, moderate and severe depression:

List A - Symptoms duration, at least of two weeks.

• Depressed mood


• Loss of interest and enjoyment


• Reduced energy level and decreased physical activities

List B

• Reduced concentration


• Reduced self-esteem and confidence


• Ideas of guilt and unworthiness


• Pessimistic thoughts


• Ideas of self-harm


• Disturbed sleep pattern


• Change in appetite and weight

Mild Depression

• At least any 2 symptoms from List A and


• 2 symptoms from List B

Moderate Depression

• Any 2 symptoms from List A and


• Any 3 symptoms from list B

Severe Depression

• All 3 symptoms from List A and


• At Least 4 symptoms from List B

However, in clinical practice, it is the change in level of functioning at social, professional and family level should remain a guiding principle of severity besides the above.

It is also useful for the patient as well as the treating doctor to make use of some “easy to apply” questionnaires, which not only help in monitoring the progress of the patient but also to gain insight in the various symptoms and behavioural changes that one can expect in depressive illness:

1. The Hospital Anxiety & Depression Scale – Zigmond & Smaith, 1983


2. Beck Depression Inventory, Aaron T Beck, 1961


3. 17 item Hamilton Depression Rating Scale (HAM-D), M Hamilton, 1967


4. Pierce Suicide Intent Scale, for use only after a suicide attempt, 1977

Treatment Options

Once the diagnosis of depression has been established, the next step is to decide whether the patient can be treated as an out-patient by you, a GP or he/she needs to be referred to the specialist services. The decision is usually based on the severity of symptoms and the views of the patient and his/her main caregiver.

Patients with severe depression and psychotic features, where they may be at risk to themselves or others, are best referred to the local mental health services for further assessment and treatment. Usually such patients will need in-patient treatment and occasionally they may require admission under the Mental Health Act, 1983.

The patients with mild to moderate depression are normally managed as out-patients by GPs and/or the community mental health team staff.

There are essential 4 key steps in managing depression in the community:

Step 1 Diagnosis and Investigations

Step 2 Briefing and Involvement of other key members of family/partner

Step 3 Non-pharmacological treatment of Depression

Step 4 Pharmacological treatment of Depression

Step 1

The first step in management of depression should constitute the following:

• Explanation to the patient why you think that he/she may be suffering from depression


• What are the likely aetiological factors – genetics, biological, social and psychological


• What are the further investigation to be carried out and why? In keeping with the patient’s age and clinical symptoms, you may consider the essential haematological and biochemistry investigations including thyroid functions, PSA, X-ray chest, ECG and CT Brain Scan

The first consultation should end with the patient being reassured and better informed. The patient is also advised to bring along their key caregiver/partner to the next consultation.

Step 2

The second consultation should include the following:

• Gathering of additional information from the key members of the family/partner.


• Inform the patient of the results of the investigations


• Carry out a brief physical examination, if not already done so


• Complete any depression questionnaires that you may consider necessary – Beck Depression Inventory (BDI – A Beck, 1961) and the Hospital Anxiety and Depression Scale (HAD – Zigmund & Smaith, 1983)


• The key caregiver/partner may also be asked to complete the questionnaires on the patient’s condition in order to obtain their understanding of the patient’s condition. This allows a patient and the family member further insight into the various presenting symptoms. The benefit of the patient’s partner also scoring the patient on BDI and HAD is twofold. The first to make him/her understand that the patient’s symptoms constitute a clinical diagnosis of depression; and if there is significant difference in the overall scores between them, then this is an ideal opportunity for them to learn and empathise with each other. This is often the beginning of Inter Personal Psychotherapy (IPT), which is important in treating patients with depression.

The theory of IPT is based on the principle that the symptoms of depression are the result of relationship difficulties and resolving these difficulties, as well as attitudes to self and others will improve most symptoms of mild and moderate severity.

Effectively, by this stage, you have established the clinical diagnosis of depression and its severity. You have also excluded any underlying occult physical pathology responsible for the patient’s symptoms. You have explained, informed and reassured the patient about the presenting symptoms and that they are treatable. Above all, you have involved the patient’s main caregiver/partner in the management of your patient. Also, without you realising, you have developed a “Therapeutic Alliance,” trust and confidence with your patient as well as with the caregiver/partner.

Outline your plans to treat the patient, which should include details about the following:

1. Non-pharmacological treatment


2. Roles and responsibilities of the patient


3. The pharmacological treatment


4. Follow up arrangements

Step 3 - NON-PHARMACOLOGICAL TREATMENT OF DEPRESSION

With regard to the non-pharmacological treatment of depression, I suggest the following:

• Physical activities


• Balanced nutrition and healthy lifestyle


• Improved sleep pattern


• Reducing and modifying of stressors


• De-stressing activities i.e., relaxation, yoga, meditation, etc


• Supportive, cognitive, interpersonal and marital psychotherapy


• Advice and support in managing young children


• Advice and support in managing household and financial matters

Step 4 - PHARMACOLOGICAL TREATMENT OF DEPRESSION

Before prescribing any medication, it is useful to inform the patient of the following:

• Which antidepressant you are going to prescribe and why


• How long it would take to improve the patient’s symptoms


• What side-effects may or may not be experienced and what to do about them

Following is a brief summary of antidepressants that are currently available in the UK market and some guidelines on how to choose the most appropriate:

British National Formulary (BNF 2007) lists currently available 26 antidepressants under four broad categories:

Tricyclic Antidepressants

• Amitriptyline


• Clomipramine HCL


• Dothiepin HCL


• Doxepin


• Imipramine


• Lofepramine


• Nortriptyline


• Trimipramine

Related Antidepressants

• Mianserin HCL


• Trazadone HCL

Monoamine-Oxidase Inhibitors (MAOIs)

• Phenelzine


• Isocarboxazid


• Tranylcypromine

Reversible MAOIs

• Moclobemide

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Citalopram


• Escitalopram


• Fluoxetine


• Fluvoxamine


• Paroxetine


• Sertraline

Other Antidepressants

• Duloxetine


• Flupenthixol


• Mirtazapine


• Reboxetine


• Tryptophan


• Venlafaxine

In General Practice almost all patients with mild to moderate depressive illness without active suicidal intent and psychotic symptoms can be managed with only four of the above listed antidepressants. It is better to learn well about a few antidepressants rather than trying different ones with limited experience and knowledge.

1. Citalopram


2. Fluoxetine


3. Mirtazapine


4. Duloxetine

PRESCRIBING AN ANTIDEPRESSANT

Before writing a prescription, ask these questions again:

1. Can the patient be treated with non-pharmacological methods of treatment? (Mild Depression)


2. Can the patient be safely treated as an out-patient? (Mild to Moderate Depression without active suicidal intent and good social support)


3. Should the patient be referred to the community and/or in-patient mental health services because he/she is severely depressed with active suicidal intent and/or psychotic symptoms, Bipolar Mood Disorder, poor compliance and absence of social support network, depression with other psychiatric disorders such as schizophrenia, drug and alcohol abuse and dementia.

Also, consider the following:

• Social and other circumstances – can the patient manage with her children or does she need help in this regard?


• Should the patient continue to work or would he/she benefit from time off work?


• What are the current stressors – finance and relationship issues – can they be modified?

The following would further help to decide which antidepressant to choose:

• Previous response to a particular antidepressant


• History and treatment of depression of other members of immediate family with a particular antidepressant


• Patient preference and the reasons


• Safety in overdose


• Interaction with other prescribed medications


• Current most troublesome symptoms, such as sleep problems, restlessness and agitation, anxiety and panic attacks with other symptoms of depression

SUGGESTED PRESCRIPTION FOR MILD DEPRESSION

• Physical activity for 30 minutes daily such as a brisk walk to the point that one perspires mildly. It is at this point that the patient’s brain will release natural endorphins, which are mood elevators and painkillers.



• Balanced nutrition – reduce alcohol and smoking to the minimum and a diet of plenty of fruit and vegetables with fish and chicken is ideal. If necessary, refer the patient to a local nutritionist for further advice.



• Organise help with children at home and minimise other stressors such as housing and financial issues.



• Supportive and marital psychotherapy, if necessary through the Practice based counsellor or Private/NHS psychology services.



• Advice on yoga and meditation for specific de-stressing activities. Some patients would prefer relaxation through breathing exercises, swimming, acupuncture, etc.



• Specific problem solving advice from the Department of Housing and Social Services for accommodation and financial help and support in managing bills and other debts.



• The patient may prefer to continue to do his/her job as this often provides a little extra help from being with colleagues and not simply being alone at home.



• See your patient weekly and within 3-4 weeks the patient will show signs of improvement.



• Sometimes, you may need to consider a small dose of night sedation if sleep is a problem or remains a problem, such as Zopidone 3.75 mg or Temazepam 10 mg nocte.

If after 4-6 weeks, there is no improvement then consider adding a small dose of SSRIs.

Consider prescribing Citalopram 10 mg daily after breakfast gradually increasing to 20 mg daily after 3-4 days. By starting with a small dose of 10 mg you avoid the side effects such as nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, increased anxiety, headaches, insomnia, tremor and dizziness.

Continue the antidepressant for six months after full recovery in case of first episode. As the symptoms improve, the patient should be encouraged to come off the night sedation.

SUGGESTED PRESCRIPTION FOR MODERATE DEPRESSION

In cases of depression of moderate severity, consider starting the antidepressant as the first line treatment with advice regarding the various non-pharmacological treatment options and introduce them as and when practically possible and the patient is ready to try them out.

• Citalopram 10 mg daily after breakfast for 3-4 days and then increase to 20 mg daily after breakfast.



• If necessary, add night sedation, say Zopidone 3.75 mg nocte or Temazepam 10 mg nocte.



• If restlessness and agitation are a concern to the patient, then add a small dose of antipsychotic such as Quetiapine 25 mg nocte or Risperidone 0.5 mg to 1.0 mg nocte.

The patient will start showing some improvement within 2-3 weeks especially in his/her symptoms of insomnia, anxiety and energy level. Thereafter improvement will be noticed in mood, motivation and confidence level.

Continue the antidepressant for 6-12 months after full recovery and thereafter, you may consider reducing the dose and gradually withdrawing it over a period of 3-6 months.


In case of no response to antidepressant after six weeks, consider the following:

• Review the diagnosis


• Check the patient compliance


• Make sure that there are no other concurrent physical or psychiatric disorders that need further investigations and treatment.


• If there is partial response, consider increasing the dose to Citalopram 30 mg and continue to increase upto 40 mg after breakfast.


• Re-evaluate the patient’s environmental stressors and advise accordingly. Make sure that the relationship issues are carefully addressed and the patient is fully understood and supported by the members of his/her immediate family.

If, say after another 3 weeks there is still no response, then consider switching to another antidepressant.

SWITCHING TO ANOTHER ANTIDEPRESSANT

Here we have the choices of four other antidepressants

• Fluoxetine


• Escitalopram


• Mirtazapine


• Duloxetine

FLUOXETINE

If the patient is significantly troubled by the symptoms of Bulimia and/or Obsessive Compulsive Disorder, then consider replacing Citalopram with Fluoxetine 20 mg daily increasing 40-60 mg daily over a period of 4-6 weeks.

ESCITALOPRAM

If the patient is significantly troubled by the symptoms of generalised or specific social phobic anxiety with or without panic attacks, then consider using Escitalopram in doses of 5 mg to a maximum of 20 mg daily after breakfast.

MIRTAZAPINE

If the patient is significantly troubled by poor sleep pattern then consider the use of Mirtazapine, starting with 15 mg nocte and gradually increasing to a maximum of 45 mg nocte.

Look out for increase in appetite and weight gain, excessive sedation, oedema and less commonly, headaches, dizziness, arthralgia, akathesia, rash and reversible agranulocytosis.

DULOXETINE

Duloxetine is classified as Serotonin and Noradrenaline Reuptake Inhibitor (SNRI), similar to Venlafaxine but without any serious cardiac side effects. It is about 5 times more potent in inhibiting the reuptake of serotonin than that of noradrenaline.

If the patient is presenting with significant symptoms of lethargy, low energy level, lack of motivation, withdrawn with lowered mood, then consider using Duloxetine 30 mg nocte increasing to 60 mg nocte.

Duloxetine does not have the side effects of sexual dysfunction as is in the case of most SSRIs.

Watch out for the side effects of nausea, vomiting, dyspepsia, diarrhoea, insomnia, headaches and dizziness.



A combination of two antidepressants could be safely considered in General Practice. The only combination that could be considered would be Citalopram and Mirtazapine. When the patient has initially responded to Citalopram but has been troubled by major sleep disorders, a combination of Citalopram 10-20 mg mane and Mirtazapine 15-30 mg nocte may be considered.

If there is no response to at least two different antidepressants, you should consider referring the patient to the local mental health services.

Treatment of severe depression with active suicidal intent and psychotic features should be dealt with by a specialist team as an in-patient and will be described elsewhere.

Author:
Dr Satvir Singh
FRANZCP (Aust), FRCPsych (UK), MSc (Lon), MRCPsych (UK), DPM, MBBS
Consultant Psychiatrist & Lead Consultant for Undergraduate Medical Education (Psychiatry)
Kent & Medway NHS and Social Care Partnership Trust
Canterbury, Kent

References:

1. ICD-10, WHO, 1992
2. DSM-IV, AMA, 1994
3. Oxford Handbook of Psychiatry, Semple D, et al, 2005
4. Core Psychiatry, Second Edition, Wright P, et al, 2005
5. Companion to Psychiatric Studies, Eve C Johnstone, et al, 1998
6. Shorter Oxford Textbook of Psychiatry, Fifth Edition, M Gelder et al, 2006
7. MIMMS Handbook of Psychiatry, 3rd Edition, Janssen Cilang, 2006
8. BNF, Sept 2007
9. Stress, Anxiety and Depression, Burrows G, et al, 1999
10. The Maudsley, Prescribing Guidelines, 9th Edition, Taylor D, et al

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