Depression is one of a group of disorders known as the effective mood disorders, and the internalising disorders other examples

s include: Affective mood disorder Depression Anxiety Bipolar Disorder The symptoms of these conditions are very similar, and there is considerable overlap. The actual combination of symptoms will determine the diagnosis.

Depression
This can occur as a single episode, or as ongoing condition with periods of relapse and remission. Depressed patients have a decreased quality of life, as well as increased mortality. Aetiology Genetic susceptibility Life factors i.e. social situation e.g. single mums Alcohol/drug dependence Abuse (sexual or not) particularly in childhood Unemployed Previous psychiatric diagnosis Chronic disease Lack of a confiding relationship Urban population Post natal (10% of all women who give birth!) Epidemiology 10-16% of men, and 20-24% of women will have some symptoms of depression 2-4% of men and 7-8& of women will have actual depression It is the most common GP diagnosis and accounts for about 12% of all new illnesses It accounts for 45% of all psychiatric diagnoses Differentials for low mood Hypothyroidism Bipolar disorder Cancer / terminal diagnosis Investigations FBC U+Es Haemotinics folate and B12 LFTs for alcohol / drugs / cancer CXR to look for chronic infection (e.g. TB) ECG can show up metabolic disturbances Mental state FULL HISTORY!

Major Symptoms the three core symptoms Low mood Anhedonia does not take any pleasure from any activities (or reduced pleasure from normal activities). Low energy levels We say depression is present when 2 or more of these symptoms exist for more than 2 weeks. more than 2 weeks means that the patient would have experienced the symptoms for at least part of the day on everyday for the last two weeks. Minor symptoms Cognitive o Feelings of guilt, uselessness, worthlessness o Thoughts of SUICIDE Always ask if they say they are having suicidal thoughts if they have acted upon any of these thoughts e.g. have they started to stock up on paracetomol. o Poor concentration Functional o Sleep Difficulty getting to sleep Waking up several times during the night Early Waking This is significant if the patient regularly wakes up 2 hours before normal o Weight loss This will be because the patient is eating less, either because they take no pleasure in eating and/or because they feel nauseous. o Weight gain can also occur Patients may comfort eat Make sure you ask if the weight loss/gain is intentional! Weight change of >5% is significant. o Loss of libido. o Psychomotor retardation the patient can be very slow both in their thoughts and actions, to a degree that is noticeable by others. o Agitated and fidgety this can be both in their thoughts and physically. Patients may keep going over and over the same thoughts in their mind, or they may e.g. stand up and sit down constantly. o Memory problems people may complain of memory problems, but it is probably not their memory that is the issue. If you test them on memory things you may notice they do not concentrate when the information is first given, thus the information is not processed, and so they are not able to recall it however it is theinformation processing and not the memory recall that is at fault. Other clinical characteristics Diurnal variation of symptoms is common. Generally, symptoms are worse early in the morning and late at nightthan at other times in the day. Hallucinations and delusions these may be present, and are generally congruent to the current mood. Schneiders positive symptoms can occur in severe depression. Some patients may experience melancholia this is where the patient feels unable to experience any emotions at all emotional numbness.

o Patients will often withdraw from social activities.

Diagnosis The diagnosis of severity not only depends on the symptoms below, but also on the impact on normal functioning. An example of functioning for each level of depression is given in green. Mild depression 1 core symptom, and 3 other symptoms for at least 2 weeks Moderate Depression - 1 core symptom and 4-7 other symptoms (major or minor), for at least 2 weeks Severe depression - 1 core symptoms and 7+ other symptoms (major or minor), for at least 2 weeks. There may also be: o Psychotic symptoms o Hallucinations o Delusions The diagnosis of severity also depends on the impact on normal functioning.

o Reduced ability to perform at work, reduced willingness to socialise o able to

Screening Tools In general practice, screening tools are often used to assess if a patient is suffering from depression, as well as to track the course of the condition over time. Two examples of screening tools are: Hospital Anxiety and Depression score (HADS) (external link) despite its name is still used in general practice. Patient Health Questionnaire (PHQ-9) (external link) ICD-10 depression Inventory (MDI) (external link) Other variations may be used. Patients may complete these as questionnaires on paper, or they may complete them on the computer. The second method is more widely used, as you are able to easily and quickly compare progress over time. o These methods are able to give a rough guide to the severity f the depression, as well as to assess risk.

Questions to ask when taking a history Have you felt low or miserable recently? Have you lost your emotions? Does it happen everyday? Does anything seem to have brought it on? Have you lost interest in things you usually enjoy? Does your current mood/experience interfere with your normal life?

o Do you still see your friends often? o Sleep o Weight (loss) o feelings of guilt o feelings of worthlessness

Mental State Appearance and behaviour poor self care, lack of eye contact, does not engage in conversation, little movement, OR lots of fidgeting Speech monotone, hesitant, slow

DEAD SWAMP depression history taking made easy! If you can remember this, and ask all these questions, you are unlikely to miss any major Points: D Depressions E Energy levels A Anhedonia D Death thoughts about death and self harm i.e. Risk! S Sleep pattern W Worthlessness, guilt A Appetite M Mentation decreased ability to think and concentrate P psychomotor agitation and retardation

Post natal depression Post natal blues occurs 3-4 days after birth Post natal depression occurs about 1 year after baby Post natal psychosis can occur at any time, and involves delusions/hallucinations ECT works particularly well for these patients Electro-convulsive therapy

Treatment

Mild Depression

Moderate and severe depression Treatment-resistant, atypical/psychotic depression, those at risk High risk
Drug treatments

Watchful waiting, CBT (not usually practical on the NHS due to long waiting lists),computerised CBT, self-help, exercise, short psychological interventions Medication (see below), psychological interventions, consider getting social support Medication, complex psychological interventions, combined rugs treatment All the above, plus consider ECT

There are details about mechanisms and side effects of medications in the Psychiatric medications article SSRIs 1st line. E.g. fluoxetine, citalopram. Side effects include:

o Nausea o Vomiting

o Abdominal pain o Sexual dysfunction o Allow 4-6 weeks for beneficial effects o Patients may describe how low feelings are not as pronounced, but the drugs do not increase happy feelings. o If one SSRI is not successful, attempt another SSRI, before trying other drugs If these are unsuccessful you can consider the following types of medication:

o Tricyclic antidepressants o MAOI monoamine oxidase inhibitors o NASSA o St Johns Wort Medications are effective 70% of patients but you need to trial them for at least 4-6 weeks. If this is

unsuccessful try another drug in the same class, before trying a drug in a different class.

Cocktail phenomenon Anecdotally, doctors report that the antidepressive effect is greatest when you mix the medications together although its not in the nice guidelines. However! Be aware that you should not use MAOIs in conjunction with other anti-depressants as they can cause a serotonin syndrome. It is also recommended not to use anoth anti-depressant within 2 weeks of stopping an MAOI inhibitor.

Theories of Pathology Depression

The Monoamine theory This is widely accepted, although it isnt without its flaws. It states that depression results from underactivity of monoamine transmitters, and conversely, that mania results fromoveractivity of monoamine transmitters. The main transmitter involved is serotonin although it is thought that noradrenaline is also involved. Most serotonergic neurons arise in the Raphe area of the midbrain, and project to the limbic system and cerebral cortex. Most noradrenalin neurons are found in the locus cereleus and lateral tegumental areas of the brainstem. There are considerable links between Raphe and locus cereleus areas. Evidence for the theory comes from the fact that: There are reduced levels of 5-HT in the brains of depressed people There are increased number of 5-HT receptors in the brains of suicidal patients The theory is also generally supported by the medications used to treat the condition, although there are some anomalies. In clinical practice, both noradrenaline and 5-HT treatments are equally effective, although some people will respond better to some types of drugs than others. It is also worth noting that when patients take medications the level of the NT in the brain is altered very quickly, but theclinical effect takes weeks to appear. This tells us that there is some secondary adaptive changes in the brain which are responsible for the condition, and not just the actual level of NT present. These changes probably involve the downregulation of receptors. There are also probably altered signalling pathways in response to 5-HT in depressed patients basically G-coupling may no longer function properly.

Hypothalamic Involvement Hypothalamic neurons receive 5-HT input, which alters their output (in this case it looks like 5-HT is inhibitory of these neurons). In turn, they release CRH (corticotropic releasing hormone), which controls ACTH, and ultimately, steroid levels. In depressed patients, cortisol levels are often high, because the hypothalamic neurons are not suppressed as much as normal, and just like in Cushings, these patients will fail to be suppressed by the dexamethasone suppression test. Even more interesting is that CRH itself in excess quantities actually causes some of the symptoms of depression such as anxiety, loss of appetite, reduced activity etc. and CRH levels are also usually raised in depression. Neuroplasticity and Hypotrophy In depressed patients, there is often neuron loss in the hippocampus and prefrontal cortex. Also, many of the therapies used to treat depression, and thus ultimately 5-HT itself actually promote neurogenesis. ECT (electroconvulsive therapy) also promotes neurogenesis Many of the studies for this have so far only been conducted in animals, and thus it is still only a hypothesis.

Treatment of Depression
Summary

Drug Tricyclic antidepressants MAO inhibitors Reserpine Methotyrosie Methyldopa ECT Tryptophan
*used to help calm manic patients General effects of drug treatment Increased monoamine levels in the brain

Mechanism Block NA and 5-HT re-uptake Increase stores of NA and 5-HT Increase NA and 5-HT storage Inhibits NA synthesis Inhibits NA synthesis Increases CNS responsiveness to 5-HT and NA Increases 5-HT synthesis

Effect Mood Mood Mood Mood* Mood* Mood Mood

Reversed damaged intracellular signalling pathways Reduced CRF production Inhibition of NMDA release

There are details about mechanisms and side effects of medications in the Psychiatric medications article

ECT electroconvulsive therapy Still controversial, ECT has been proven in several studies to be more effective than antidepressant medications! Mechanism It is thought that it induces grand mal type seizures, and that these are necessary for anti-depressant effect. It is also thought that seizures that originate in lower brain areas are less effective than seizures that originate in higher brain areas at reducing depression.

Using a high electrical current increases the therapeutic effect, but increases the risk of memory loss and confusion.

o Unilateral treatment to the non-dominant hemisphere also reduces the risk of confusion and memory loss, but again has reduced efficacy. Patients who undergo this type of ECT require 2-4 more sessions than other individuals. o Sub-seizure currents do not have therapeutic benefit. ECT increases the activity of 5-HT cell, and increases the number of post-synaptic 5-HT receptors. It also enhances dopamine activity, and has similar effects on noradrenaline to anti-depressant drugs (particularly reduction in receptors). Clinical use ECT is mainly used in severe depression. It is mostly reserved for depression that fails to respond to drug intervention. It is particularly effective in illness that has: Psychomotor retardation Early-morning wakening Psychotic features Severe weight loss It is also used controversially in: Schizophrenia with severe depressive symptoms Schizophrenia with Clouding of consciousness Mania; when drug treatments (both neuroleptics and lithium) have been ineffective

Practicalities It is given under a short acting general anaesthetic. Patients are also given a muscle relaxant to reduce the risk of injury. Patients are usually starved from at least midnight the night before. They are also given Atropine (anticholinergic) to reduce salivary and bronchial secretions, and to prevent bradycardia. Before the treatment begins, patients are ventilated with 100% O2. This has been proven to reduce amnesia. Electrodes are placed: Unilateral one on temporal region, one near vertex Bilateral on each temporal region They are moistened to allow good contact with the skin. Almost all patients have bilateral ECT. Regimen 2x per week until improvement is seen This is usually after 6-8 treatments Unwanted effects ECT is relatively safe, but there is a mortality associated with it (1 in 20,000). However, this is extremely low, roughly equal to that of a minor procedure involving a short-acting general anaesthetic (e.g. some dental treatments). Physical complications General physiological effects include; increase in BP, massive increase in cerebral bloodflow, altered pulse rate. This means that ECT is contraindicated in patients with previous MI, arryhtmias, aneutysms, previous cerebral haemorrhage and raised ICP.

Although rare, serious physical complications can include: MI Cardiac arrhythmias PE Pneumonia Dislocations and fractures in cases where the muscle relaxant was not administered correctly or was ineffective Increased BP during treatment can cause o Cerebral haemorrhage o Bleeding of peptic ulcer Psychological side effects Mania results from 5% of cases of ECT. This is a similar risk to anti-depressants, and occurs in those at risk of bipolar disorder Confusional state occurs in almost all patients, but only lasts about an hour. May be associated with headache Memory loss there is usually both retrograde amnesia (cant remember what happened just prior to treatment) as well as anterograde amnesia (unable to lay down new memories for a short time after the procedure. Some patients may report difficulty recalling previously well-known materal e.g. telephone numbers, although in objective tests, there is no obvious problems. Factors that increase the risk of memory loss include: o Bilateral shock, shock to dominant hemisphere o >12 treatments o >3 treatments per week, with <48 hours between treatments o Not giving O2 before treatment o Using large current ECT is useful in the short-term, but does not give an indication as to what treatments might be useful in the longer term. TMS transcranial magnetic stimulation this does not provide proven benefit in depression, nor does electrical stimulation of the vagus nerve.

Risk
Managing risk is important in depression. The risk to others is usually low, but risk of self-harm is increased. You need tospecifically ask about thoughts of self harm and suicide.As well as active self harm, many depressed patients suffer self neglect, secondary to the core symptoms of depression (loss of interest in normal activities). In many cases, this can be managed with carers and home support, but in severe cases, where the patients physical well-being is at risk, then inpatient care may be necessary.

Prognosis
Prognosis for depression is very good. Most patients will make a good recovery. The greatest risk is usually death from suicide before treatment has had time to take effect. Outcome and timescales are very varied, but many patients on anti-depressant drugs will be symptom free within just 4-6 weeks. However, treatment should be continued for a minimum of 9 months, otherwise there is an 80% risk of relapse. Even despite this, recurrence is common, especially in those with previous depressive

episodes in the last 5 years. Clinicians have to make decisions on an individual basis as to whether or not to continue treatment beyond the 9 month period. Factors that point to a good outcome are: Large loss event precipitating the depression Normal pre-morbid personality