Depression

From Ganfyd

Not the same as unhappiness

Introduction

70% of women and 40% of men in the UK have experienced clinically significant depressive symptoms by age 65 (Bebbington et al, 1989)

Approximately 1 in 4 suffers a depressive illness meeting ICD-10 criteria, at some time in their life. The peak period of onset is between 25 and 50, but it may occur at any age including in children.

• 2% prevalence of “pure” depression
• 8% prevalence of mixed anxiety & depression
• The exact number with symptoms but not enough for diagnosis is unknown, but they may still have impaired function at home and work or medically unexplained symptoms (MUPS)
• Female : male = 2 : 1 [cf bipolar disorder 1 : 1]

On average, GPs in the UK see one person per day with depression, which amounts to around 2 million encounters per year. True depression differs from general feelings of sadness or grief, which affect everybody from time to time, and has categories that range from mild to moderate and severe.

In an average GP's list of around 2000 patients

Prevalence: 480 depressed patients
Incidence: 120 consult their GP in a year
3 suicide attempts each year
A suicide occurs every 7 years

Prescribing of anti-depressants increased sharply in the decade from 1995 to 2005, particularly following the introduction of fluoxetine and other SSRIs. In the UK the NHS spend on antidepressant drugs was around £400 million in 2005.

Deliberate self-harm (DSH) is about 20-30 times more common than suicide.

There are about 5000 suicides each year in England and Wales, of which 400-500 involve overdoses of antidepressant. This stresses the importance of care in the quantities of medication prescribed in the early phase of treatment and choosing safer SSRI’s and SNRI’s in preference to TCA’s. Some completed suicides will have consulted their GP with non-specific symptoms in the weeks before and may use prescribed drugs to carry out their intent, whether threatened or not.

Aetiology

70% of depressive episodes are preceded by life events. There is a relationship between the stress of the event and the likelihood of a depression being precipitated. However, life events per se make only a partial contribution. Other important interactive factors include: premorbid personality style, cognitive style, FH of mental illness, drug & alcohol use, neurochemical disturbance, work and social stability, living alone or with significant other and social support available at time of crisis, both professional and personal.

Clinical

SUBDIVISION OF DEPRESSION

UNIPOLAR -- BIPOLAR <<<<< Only dichotomy widely supported

NEUROTIC -- PSYCHOTIC

PRIMARY -- SECONDARY

ENDOGENOUS -- REACTIVE

Types of Depressive episode

• Mild or Moderate, with or without somatic syndrome;
• Severe depressive episode without psychotic symptoms;
• Severe depressive episode with psychotic symptoms;
• Atypical depression: ill for many years, anxiety, labelled hysterical, respond to MAOI;
• “masked” depression = smiling depression;
• Recurrent depressive disorder (with/without somatic syndrome, psychotic);
• Recurrent brief depressive disorder;
• Dysthymia ( =chronic low grade depression for 2years+ , "neurotic", poor prognosis);
• Double depression – severe depressive episode + dysthymia, earlier age of onset, more severe episode later, more anxiety;
• Depressive episode, unspecified (NOS)

Related conditions: (there are large overlaps)

• Anxiety disorder esp panic attacks, obsessive-compulsive disorder(OCD);
• Post-traumatic stress disorder(PTSD);
• Adjustment disorders, such as Brief depressive reaction;
• Bipolar affective disorder: Bipolar I – mania, hospitalised; Bipolar II – hypomania, sometimes secondary to anti-depressants, not hospitalised;
• Cyclothymia (rapid mood swings every few weeks);
• Mixed affective episode (curious mix of mania + depression at same time);
• Post-schizophrenic depression (post-any psychotic episode include drug induced);
• Harmful use, Dependence, withdrawal states from drugs & alcohol;
• Depressive psuedodementia

CLINICAL FEATURES OF DEPRESSION

TYPICAL SYMPTOMS

• Depressed mood – pervasive, longer than 2 weeks;
• Loss of interest and enjoyment;
• Reduced energy and easy fatiguability

OTHER COMMON SYMPTOMS

• Reduced concentration and attention (become clumsy);
• Reduced self-esteem and self-confidence;
• Ideas of guilt and unworthiness;
• Bleak and pessimistic views of the future;
• Irritable and easily frustrated;
• Ideas or acts of self-harm or suicide;
• Disturbed sleep;
• Diminished appetite ( or sometimes comfort-eating)

Somatic Symptoms

• Anhedonia;
• Loss of emotional reactivity (numbness, indifference);
• Early morning wakening (2 hours or more before usual time);
• Hypersomnia (in some);

Abrupt waking to alertness, followed by lying awake brooding, is the classic pattern

• Diurnal variation in mood (eg worse in the morning for hours);
• Psychomotor retardation or agitation (both can suddenly lead to impulsively self-harming behaviour);
• Loss of appetite;
• Loss of weight (5% or more of body weight in past month);
• Loss of libido;
• Menstrual irregularities;
• Constipation which may be objective, or a manifestation of a feeling that there is something bad inside.

TYPES OF PRESENTATION

• Tired all the time (TATT), increasingly lethargic;
• "My partner told me to come and see you" etc;
• "cannot be bothered anymore";
• Stopped working due to "stress", needs a sick note;
• Somatisation, repeated investigation with no cause found for "problem" etc;
• Medically unexplained symptoms (MUPS) e.g whole body pain, "heavy stomach", "keep getting butterflies for no reason doctor";
• "I’m depressed";
• "I got the sack for falling asleep at work";
• "I keep thinking about ending it all";
• Worsening OCD symptoms;
• Anxiety symptoms;
• Depression may be actively denied;
• Chinese women tend to present with worries about their children, offering nothing of their own feelings.
• Etc

Don’t rush to treat with drugs. Mild depression is a normal experience; people often have perfectly valid reasons to be down. Try optimising the patient’s personal resources, problem solving and motivational interviewing before drugs.

Screening for depression

The aim of screening questions is to rapidly identify those in whom further enquiry is necessary, and also those where depression is very unlikely.

Two validated questions:

1) During the last month, have you been bothered by feeling down, depressed or hopeless?

2) During the last month, have you often been bothered by having little interest or pleasure in doing things?

Patients answering 'Yes' to either question need further enquiry, although not all will have depression. Patients answering 'No' to both questions are very unlikely to have depression. However, listen to your body. If the patient makes you feel sad, they probably are.

Quick Diagnostic Checklist For Depression

The presence of five of the DSM–IV criteria for depression, indicates major depression. Below is a simplified version for use in primary care.

The DSM-IV Criteria

Over the last 2 weeks, five of the following features should be present, of which one or more should be:

• Depressed mood
• Loss of interest or pleasure

And the remaining (the total to make at least five) from any of the following:

• Significant weight loss or gain or an increase or decrease in appetite.
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness or excessive guilt
• Diminished ability to think or concentrate
• Recurrent thoughts of death (not just fear of dying) or recurrent suicidal ideas.

Measuring Severity of Depression

In general terms, severity of depression is assessed by both the nature and number of depressive symptoms reported, and also the degree to which normal functioning is impaired. The distinction between mild episodes of major depression and more severe episodes has particular implications for the management options recommended by NICE.

Assessment tools for rating severity

There are a range of assessment tools that can be used to measure severity. Some of these have been validated in different settings, such as in primary care. Absolute scores are not necessarily as clinically useful as the change in scores between appointments.

Patient-completed scales

These are completed by the patient, typically before seeing the doctor. Those shown here have been validated for use in primary care settings.

The PHQ-9 tool can be downloaded from Pfizer under these terms of use: terms of use from Pfizer

BDI - the Beck Depression Inventory. Must be purchased from Harcourt Assessment.

HADS - the Hospital Anxiety and Depression Scale. Purchased from nfer-nelson

Doctor-completed scales

These are completed by the doctor, following the usual processes of clinical assessment. The most-commonly used in research settings are the HAMD and MADRS scales. A shortened, seven-item version of the HAMD has been validated for use in primary care.

HAMD-7 validation

Investigations

Comorbid physical illness should be actively sought. Many organic disorders are associated with depression either as part of their symptomatology or as a psychological reaction to the disease.

Blood tests

Investigations considered in the diagnosis of depression:

FBC, Red cell folate, Vit B12, U & E’s, Blood sugar, Thyroid function, Liver Function Tests, Weight (BMI), Blood pressure, Other investigation where clinically indicated.

It must be born in mind that to investigate is to risk reinforcing somatising behaviours.

Treatment

Treatment

Psychological

Cognitive Behaviour Therapy (CBT) has been demonstrated to be an effective treatment for depression. However, it is not always available in primary care, it is relatively expensive (cost per course £100 -£160) and there may be a long waiting time. Refer via Community Mental Health Team as some CPN’s are specially trained in CBT. Alternatively refer to Consultant-led CBT Services if available, but waiting lists are 12-18 months. The patients have to be psychologically-minded and usually those with recurrent depression are more suitable as the course of their illness can be dramatically changed. Interpersonal psychotherapy may be offered in some Mental Health Trusts and has some proven efficacy with depressed patients. Both this psychological therapies appear to work best with patients of the YAVIS type ie Young, Attractive, Verbal, Intelligent, Solvent. There is no research evidence that Supportive Counselling or Brief psychodynamic therapy are of any benefit in terms of outcomes in depression.

CBT is a treatment that should be considered and may be offered to the patient, especially where there is concern about the side effects of drug treatment.

Referral of any depressed patient for specialist care by CPN/Psychiatrists/Hospital should be considered in the following circumstances:

High risk of suicide

Failure to respond to usual treatment (2 maybe 3 antidepressants)

Diagnosis difficult

Comorbid conditions in which the other illness or its treatment makes the treatment of depression problematic (for example serious physical illness or personality disorder)

Patients with psychotic depression who may require either combinations of different antidepressants or ECT.

Patients with bipolar disorder who represent a higher suicide risk during depressed phases and may need careful monitoring of lithium concentration.

Patients who become hypomanic/manic for the first time immediately after anti-depressant treatment (?Bipolar II)

Patients with little social support and who are the main carer for a sick relative or young children.

Associated complex Drug and/or Alcohol problems.

Following a serious attempt at suicide or repeated DSH when depressed.

Pharmacological

The SSRIs are the drugs of first choice for depression in patients with the following chronic conditions:

Cardiovascular disease Hepatic disease Renal disease Neurological disorders Diabetes (except Fluoxetine)

SSRI have recently been found to have an antiplatelet effect similar to Aspirin so caution is advised in patients with a history of GI bleeding. Use lowest effective dose or consider Mirtazapine, Trazodone or Reboxetine.

Selective serotonin reuptake inhibitors

See Selective Serotonin Reuptake Inhibitors (SSRIs):.

SSRI Adverse effects: Nausea, diarrhoea, agitation, insomnia, dry mouth & blurred vision, hyponatraemia, sexual dysfunction (male & female), slighly lowers seizure threshold so caution in epilepsy. 10% of people stop taking them because of side effects.

Fluoxetine is safer in overdose than tri-cyclics. It is less sedative and has fewer side effects. It should be noted however, that SSRIs can provoke an initial increase in symptoms of anxiety for first few days. Symptoms of anxiety may be of relevance in this case and careful counselling of the patient with an explanation of the initial side effects and the lag time of action (2 weeks) is important in all cases.

Paroxetine – also for OCD, PTSD, Panic, Social phobia, try to avoid as sedation, orofacial dystonias and withdrawal effects common. Not to be used <18 years.

Sertraline – prevention of relapse, OCD, PTSD; contraindicated in Liver disease/failure, nausea less common.

Citalopram – panic, prevention of relapse; less nausea, few interactions hence better choice for elderly or polypharmacy.

Serotonin noradrenergic reuptake inhibitors

See Selective Serotonin & Noradrenaline Reuptake Inhibitors (SNRIs):.

Use as second line following poor response to SSRIs. Should only be initiated in Secondary Care unless you have Special Interest Training such as GPwSI. Venlafaxine is good for Generalised Anxiety Disorder too. The therapeutic dose of Venlafaxine should be 75mg bd except in the elderly when 37.5 mg bd is reasonable. A reasonable starting dose is 37.mg bd for 3-7 days to aid tolerance of side effects, then rapidly increase after about 1 week to 75mg bd. After 2-4 weeks consider changing to Venlafaxine XL (Effexor XL) 150mg od at whatever time of day the paient prefers. If there is persisting depression, try 225mg od but consider referring to a Psychiatrist at this stage. Doses of 225mg or higher may raise BP, so monitor BP and consider another antidepressant in hypertensive patients.

Although Venlafaxine has a similar side effect profile to the SSRIs (Fluoxetine, Paroxetine), the cost is at least twice as much for a comparable course.

Duloxetine may be a practical alternative to venlafaxine, and since the initiation of the latter by GPs was discouraged in 2005 may become more commonly used.

Similar acting NASSAs which also increase serotonin and noradrenaline are worth considering in primary care. Mirtazapine (Zispin) is good for thin, agitated, anxious, poor sleepers as its side effect profile causes some weight gain, mild sedation and much less nausea and agitation compared to SSRI’s. Sexual dysfunction is very rare, if having to stop an SSRI.

Trazodone, related to TCAs – treats depression where sedation required, calming, safe, nausea but fewer anti-muscarinic and cardiovascular effects. Liquid available. Rarely priapism develops, discontinue immediately.

Monoamine oxidase inhibitors

See Monoamine oxidase inhibitors (MAOIs):.

Phenelzine – leave for specialists, often 2nd/3rd line, as a rule do not start until 2 weeks after stopping ANY other anti-depressant, 5 weeks if Prozac; avoid tyramine-based foods and ephedrine based drugs/cough mixtures etc Moclobemide (Reversible inhibitor of Monoamine oxidase type A = RIMA), less potentiation of the pressor effect of tyramine.

Noradrenaline reuptake inhibitors

See Noradrenaline Reuptake Inhibitor (NARI):.

Reboxetine – maintainence of improvement, improves social functioning, not really used much as insomnia, sweating, dry mouth, constipation and urinary hesitancy/retention happen too commonly.

Tricyclic antidepressants

See Tricyclic antidepressants (TCAs):.

Some e.g Clomipramine are more effective than SSRI’s. They are cheap and effective especially in severe depression, those patients with chronic pain or sleep problems. They are being used much less in the last 10 years as they are dangerous in overdose. 300 TCA deaths per year and people on them are 5 times more likely to be involved in Road Traffic Accidents. They should be avoided in cardiac illness and dementia. Because of their side effects 80% of people are given low doses which are then inadequate to treat depression effectively (and unsafe in overdose).

Try to avoid prescribing Dothiepin as this drug is dangerous in overdose, as with the other tri-cyclics, it can cause cardiac arrhythmia. If there is a high risk of self-harm, it would be preferable to use other drugs.

Non-response to antidepressant medication should not be assumed until 6-8 weeks of treatment have failed to produce a response. The patient must be encouraged to take medication daily, and not to miss doses. Explanation of the lag time (two weeks minimum) before treatment takes effect helps to avoid non-compliance. They must be encouraged to take medication regularly and not to miss doses. Changing anti-depressants should not be considered until there has been non-response over a period of 6-8 weeks.

All patients should continue for 6 months on an antidepressant after remission following acute treatment. Patients with more than two episodes of major depression should have maintenance treatment for at least 5 years.

Glutamate modulators

A large number of drugs that modulate glutamate neurotransmission show some promise, usually as adjudicative therapy for symptoms such as anxiety. They are often used as mood stabilizers in bipolar depression although here it is known that lithium and valproate are less effective in preventing depression than mania. Popular presently is lamotrigine^[1].

Surgical