Medication used for Depression (Advanced)

Week 3

Context

Depression is a normal response to loss or misfortune, when it may be called grief or mourning. Depression is abnormal when it is out of proportion to the misfortune, or is unduly prolonged.

Depression is one of the most common psychiatric illnesses, with an annual incidence in the UK of approximately 5%. It is Predominantly treated in primary care setting, and is associated with poor quality of life for both sufferers and carers. It is associated with significant morbidity & mortality (mostly suicide), consuming large amounts of healthcare resources

Content

The rule of halves can be applied to depression: only half of people with depression will seek help from their doctors, and only half will be correctly diagnosed as being depressed. Of these, half receive treatment with an antidepressant, of whom, only half complete a course of treatment. In all, less than 10% complete a therapeutic course of treatment.

ICD-10 Criteria for ‘Depressive Episode’

Diagnostic criteria for depression ICD-10 uses an agreed list of ten depressive symptoms. Key symptoms:

persistent sadness or low mood;and/or
loss of interests or pleasure
fatigue or low energy

at least one of these, most days, most of the time for at least 2 weeks. if any of above present, ask about associated symptoms:

disturbed sleep
poor concentration or indecisiveness
low self-confidence
poor or increased appetite
suicidal thoughts or acts
agitation or slowing of movements
guilt or self-blame

the 10 symptoms then define the degree of depression, and management is based on the particular degree

not depressed (fewer than four symptoms)
mild depression (four symptoms)
moderate depression (five to six symptoms)
severe depression (seven or more symptoms, with or without psychotic symptoms)

Symptoms should be present for a month or more and every symptom should be present for most of every day. See Examples Of Common Behaviour Changes for more information about depression.

Classifications of Depression

There are many terms used to classify depression, some of which are now not being used much, as more is learned about the nature and causes of depression.

Psychotic depression: Some people who have severe clinical depression (sometimes called major depressive disorder) experience hallucinations and delusions. They are said to have psychotic depression. People who have severe clinical depression are in a depressed mood most of the day, practically every day, and can lose interest in almost everything. Mental health professionals call this sort of depression ‘unipolar’ depression in contrast to ‘bipolar disorder’, when people experience both episodes of depression and episodes of mania.

Neurotic depression: A neurotic depression is a depression in an emotionally unstable person. Secondary depressions to major personality disorders, neuroses, and drug use disorders fit the above definition. Likewise, primary depressions with a family history of alcohol (depression spectrum disease) are characterised by a long history of stormy life problems and, therefore, would fit the definition.

Endogenous v Reactive depression: The theory that depression is either 'reactive' or 'endogenous' in origin is losing support. It is now more commonly believed that both environment and genetic history play a part. 'Endogenous' is the term given to depression that has no obvious cause – that is, was not brought on by a specific life event or circumstance, but rather appears to come from nowhere. Both are related to chemical changes in the brain, however differ in terms of 'which came first – ie did the depression come first, making life's problems seem far greater than they are, or did life's problems bring on the depression? 'Reactive' depression is the term used for depression thought to be caused by a specific event or circumstance, such as relationship problems or loss of someone you love either through death or the end of a relationship, losing or changing jobs, or anything else that you find traumatic. This doesn't refer to grief, which is normal and healthy and temporary, but to depression which lasts well past the time that you would expect to start recovering from grief, and is very unhealthy.

Agitated v Retarded depression: Agitated depression is just the opposite of what usually people think depression is. Commonly people would get drained and lethargic when depressed, but in this case the feeling of irritability, anger and agitation occurs. It comes under a completely separate category with vivid symptoms and cannot be mimicked by other kinds of depression. Retarded depression is a category of depression characterised by slow thinking and behaviour.

Postnatal depression: Postnatal depression is a type of depression some women experience after having a baby. It can develop within the first six weeks of giving birth, but is often not apparent until around six months. Postnatal depression is more common than many people realise, affecting around one in 10 women after having a baby. Women from all ethnic groups can be affected. Teenage mothers are particularly at risk. The symptoms of postnatal depression are wide-ranging and can include low mood, feeling unable to cope and difficulty sleeping.

Seasonal Affective Disorder (SAD): Seasonal affective disorder (SAD) is a form of depression that people experience at a particular time of year or during a particular season. Most of us are affected by the change in seasons – it is normal to feel more cheerful and energetic when the sun is shining and the days are longer, or to find that you eat more or sleep longer in winter. However, if you experience SAD, the change in seasons will have a much greater effect on your mood and energy levels, and lead to symptoms of depression that have a significant impact on your day-to-day life. Most people experience SAD during the winter. Less commonly, some people find that they experience SAD in reverse – with depressive symptoms occurring in summer.

Recurrent Brief Depression: Recurrent brief depression, or RBD, is a relatively common mental disorder. As the name suggests, recurrent brief depression is characterised by intermittent, repetitive, depressive episodes. In order to be considered recurrent brief depression, the depressive episodes must occur between six and 12 times per year. Recurrent brief depression may present on its own, or it can be part of major depression or bipolar disorder. RBD is often seen among patients who suffer from personality disorders. Recurrent brief depression has been known to affect as many as ten percent of all individuals. The exact cause of RBD is not yet known. Scientists have long suspected a link between periods of recurrent brief depression and other mental health disorders, such as bipolar disorder. It is also thought that recurrent brief depression is hereditary. Patients with certain genetic markers are more prone to developing RBD than other individuals.

Dysthymia: Dysthymia is a milder yet more enduring type of depression that affects women two to three times more often than men. The diagnosis is given when a person has had continuous depressed mood for at least two years. For children, the duration only needs to be one year, and their mood may be irritable rather than sad or depressed. People with dysthymia may appear to be chronically mildly depressed to the point that it seems to be a part of their personality.

What medicines can cause depression?

As well as medications used to manage depression there are other medications known to be a risk factor in causing depression. These include:

Corticosteroids
Antihypertensives
Oral contraceptives
Cimetidine
NSAIDs
Opiates
Barbiturates

Principles of Effective Treatment

All antidepressants offer effective treatment for depression provided that two conditions are met:

at least a minimum effective dose is taken
treatment continues for an adequate period of time

There is usually a delay in onset of response for up to 6 weeks after starting medication, but some improvement may be seen after 2-4 weeks.In clinical trials, between 70-80% of patients respond to active treatment but about 30% will also respond to placebo – this placebo response however is rarely sustained. Following response, the antidepressant should be continued for at least 6 months, failure to do so increases risk of relapse.

Discontinuation Syndrome

The term ‘discontinuation symptoms’ is used to describe symptoms experienced on stopping prescribed drugs that are not drugs of dependence. Symptoms can include:

Agitation
Irritability
Insomnia
Vivid dreams
“flu-like symptoms”

Generally, antidepressant therapy should be discontinued over at least a 4-week period (this is not required with fluoxetine).

Response

When at least 50% of symptoms improve, we call this response. The patients are better but not well. If treatment results in removal of all symptoms, we call this remission and then recovery if this is sustained for 6 months or more. These patients are well but not cured. Every known antidepressant has the same response rate, 67% of depressed patients respond to any given medication and 33% fail to respond.

Choice of Antidepressant?

Treatment and care should take into account patient's needs and preferences. People with depression and a chronic physical health problem should have the opportunity to make informed decisions, including advance decisions and advance statements, about their care and treatment, in partnership with their practitioners. If patients do not have the capacity to make decisions, healthcare professionals should follow (in the UK) the Department of Health's advice on consent and the code of practice that accompanies the Mental Capacity Act.

Choice of antidepressant should depend on a number of factors including:

Patient preference
Experience of previous treatment(s)
Outcome of previous treatment(s)
Symptoms
Tolerability
Severity
Suicide risk
Adherence

Classes of antidepressants

Class	Examples	Possible Side Effects	Comments
Selective Serotonin-Reuptake Inhibitors (SSRIs)	citalopram fluoxetine fluvoxamine paroxetine, sertraline	Anhedonia or apathy, nausea/vomiting, drowsiness or headache, extremely vivid or strange dreams, dizziness, fatigue, pupil dilation (mydriasis), urinary retention, insomnia	Side effects are mostly present during the first week to four weeks of treatment, at a time when the body is adapting to the new medicine
Serotonin-2 Antagonist/Reuptake Inhibitors (SARI)	nefazodone, trazadone	lethargy, difficult concentrating, confusion, memory loss, uncontrollable laughter, change in libido, slurred speech, paresthesia, euphoria, tar dive dyskinesia, tachycardia, palpitations, shortness of breath, apnea, atrial fibrillation, bradycardia, ventricular activity, myocardial infarction	SARIs are antidepressants that block the reuptake of Serotonin less potently than the Selective Serotonin Reuptake Inhibitors (SSRIs) or the Tricyclic Antidepressants (TCAs). They act on Serotonin Norepinephrine and Dopamine to a lesser extent.
Selective Norepinephrine Reuptake Inhibitor (NRI)	reboxetine	Insomnia, Fatigue, Weight loss, Vomiting, Abdominal pain, Decreased appetite, Dizziness, Sleep disorders, Dehydration, Rash, Menstrual cramps, Problems passing urine, Mood swings	Consistently raising Norepinephrine levels can cause Adrenal Fatigue, where over-stimulation of the Adrenal Glands leaves them unable to meet the body’s needs to control stress.
Selective Serotonin Noradrenaline Reuptake Inhibitor (SNRI)	venlafaxine, duloxetine	Abnormal dreams, Extreme elation or feeling of happiness that may alternate with a depressed or sad mood, Engaging in dangerous or unusual activities, Hallucinations, Headache, Palpitations, High blood pressure, Hostility or aggressiveness	SNRIs are one of the newest classes of antidepressants, and their mechanism of action is on both Norepinephrine and Serotonin.
Noradrenaline and Selective Serotonin Antagonist (NaSSA)	mirtazapine, mianserin	Dry Mouth, Abdominal pain, Neck rigidity, Constipation, Thirst or dehydration, Bladder problems, Sexual problems, Blurred Vision, Dizziness, Agitation, Anxiety, Amnesia	NaSSAs are a newer type of antidepressant but have side effects such as drowsiness. Therefore it is advised to only take NaSSAs at night since they can impair daytime function.
Norepinephrine Dopamine Reuptake Inhibitor (NDRI)	buproprion	Weight loss, Headache, Dry mouth, Skin rash, Sweating, Tinnitus, Agitation, Constipation, Anxiety, Dizziness, Trouble sleeping, Muscle pain, Nausea and vomiting	Since the medication can increase blood pressure in some individuals, it’s important to monitor your levels on a regular basis. Anyone with a history of heart disease, seizure and eating disorders should alert their doctor prior to beginning an NDRI.
Monoamine Oxidase Inhibitors (MAOIs)	phenelzine tranylcypromine, phenalzine, selegiline, isocarboxazid	Blurred vision; Urinary retention; Sexual dysfunction; Mild dizziness; Muscle twitching	Second generation of antidepressants: Work by inhibiting the enzyme that speed up the breakdown of serotonin, dopamine and serotonin. Rarely used because of their unfavourable risk profile.They interact with tyramine in the body causing hypertensive crisis which can be fatal. Take emergency action if someone on MAOI show the following, severe chest pain, severe headache, sore neck, enlarged pupils, sweating with fever, vomiting, increased sensitivity to light
Reversible Inhibitors of Monoamine Oxidase (RIMAs)	moclobemide
Tricyclic Antidepressants (TCAs)	amitriptyline, imipramine, lofepramine, clomipramine, dothiapin	Cholinergic side effects: Dry mouth; Constipation; Blurred vision Other: Postural hypotension; Sexual dysfunction; Drowsiness; Weight gain; Vomiting and nausea; Cardiotoxicity

Most commonly used antidepressants are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, bupropion, and mirtazapine.

Risks with medication versus risks with no medication

Mental health practitioners have to carefully assess the need for medication, and balance the risks inherent in the medication of choice with the risk of not using medication for someone who is depressed.

Risks of medication include:

Congenital cardiac malformation esp 1st trimester; paroxetine)
Newborn persistent pulmonary hypertension (3rd trimester; SRRIs)
Neonatal withdrawal syndrome-3rd trimester; SSRI
Premature-low birth weight
Long term neurodevelopmental abnormalities
Elevated suicidal due to antidepressant use –up to the age of 25 years.
Medical-legal use of antidepressants

Risks of not medicating include:

Relapse of major depression
Increased suicidal risk due to non antidepressant use
Poor self care
Poor motivation for pre natal care
Disruption of mother infant bonding
Low birth weight, developmental delay in children of women with untreated depression
Self harm