Psychiatric disease

Psychiatric disease

Psychiatric diseases are generally thought of as disorders that disturb an individual's mental health, and include anxiety, personality, panic and eating disorders, bipolar disease, depression, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and many more. This module will address the most common of these disorders and the drugs that can be used to manage their symptoms.

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Depression

A study published in the Lancet in February 2018 found that antidepressants are more effective in patients with moderate-severe depression or major depressive disorder than placebo (see Cipriani et al. (2018)). This study reviewed results from >500 trials, that evaluated 21 different drugs, and involved >100,000 patients with depression- but note the caveat that the team could only work with the results as originally published, and experience indicates that trial results may sometimes have been analysed so as to present the most positive of outcomes. So, at least for patients with severe depression, the use of antidepressants appears to be justified. However, the majority of patients present with mild-to-moderate depression, and it is still unclear if antidepressant therapy is effective in these patients. Criticisms of the use of antidepressants in patients with milder forms of the disease are multi-fold: Are they effective in this patient group? Are they prescribed to easily and too often for mild depression? Are patients warned about the range/severity of side-effects? Are they adequately warned of the issues surrounding withdrawal? Add to this mix of concerns the subjectivity and diversity of patients' experiences and responses to the benefits and side-effects of therapy, and the efficacy of antidepressant therapy in the mildly depressed patient is obscured even further.

For information regarding the pharmacology of the antidepressant drug classes used in clinical practice see our Antidepressant drugs topic.

Depression (major depressive disorder) is a mood disorder characterised by low mood which persists for weeks or months and has a significant impact on daily life. It is a common disorder and the WHO estimates that around 5% of adults globally are affected.

Aetiology

The exact cause of depression remains unclear, but it is believed to be multifactorial with biological, genetic, environmental, and social factors all contributing. There are a number of theories about what abnormalities in the brain cause depression. One of the more prevalent is the reduction of key neurotransmitter serotonin. This is evidenced by the success of using drugs to increase serotonin levels in managing depression. However more recent theories think it is caused by a disruption in neuroregulatory systems which then has secondary effects on neurotransmitter levels. Other neurotransmitters have also been implicated such as GABA and glutamate. Environmental and social factors involved include childhood trauma and severe early stress. This leads to changes in the brain which can cause severe depression in later life. Other adverse life events can increase susceptibility as well. Genetically, depression often runs in families with high concordance seen in twin studies.

The symptoms of depression can also develop secondary to physical abnormalities such as thyroid dysfunction. Therefore, especially in persistent and hard to treat depression, it is important to screen for alternative diagnoses.

Diagnosis

A depression diagnosis is made clinically when 5 or more symptoms are present, at least one of which is low mood or anhedonia, and have a significant functional impact on daily life. Potential symptoms are listed below:

  • Persistently low or depressed mood
  • Anhedonia
  • Feelings of guilt or worthlessness
  • Lack of energy
  • Poor concentration
  • Appetite changes
  • Psychomotor retardation or agitation
  • Sleep disturbance
  • Suicidal thoughts

It is also important during the evaluation process to classify the severity of the disorder. This typically combines three elements:

  • Duration of disorder
  • Symptoms present
  • Impact on daily life

One of the most common assessment tools used is the Patient Health Questionaire-9 (PHQ-9). This is a research validated tool for identifying depression and stratifying disorder severity. Generally, a score of <16 is considered less severe and a score equal to or >16 is considered more severe.

Management

The management of depression is a stepwise approach involving a combination of lifestyle advice, pharmacological intervention and psychological therapy. Management depends on severity. A patient with a new less severe episode may be started on just a low intensity psychological intervention, while a patient with more severe depression might be started on a combination of both high intensity psychological intervention and a medication. For very severe cases of depression, electroconvulsive therapy (ECT) and other direct brain stimulating treatments can be tried. The more common management options are detailed below:

Psychological

This is a good starting point for people with mild to moderate depression as they avoid the potential adverse effects of physical treatments. However, depending on context, they may have limited availability. However, online CBT and self-help have allowed at least some of these therapies to become more widely accessed. These therapies can also be used in combination with pharmacological therapy. Different therapy options should be discussed with the patient as some may prefer either self-help, individual or group therapy.

Various types of therapy options are listed below, they are split into low intensity and high intensity interventions.

Low intensity – interventions that are lower cost and more accessible, but mostly useful in those with less severe depression.

  • Group CBT
  • Individual guided self-help
  • Physical activity programmes with a focus on mental health

High intensity – more resource intensive, can be used in isolation for those with less severe depression or in combination with medication for those with more severe depression.

  • Individual cognitive behavioural therapy (CBT)
  • Interpersonal therapy (IPT)
  • Behavioural activation (BA)
  • Short term Psychodynamic therapy (STPT)
  • Counselling

Pharmacological

All medication courses should be attempted for at least 3–6 months with patients being counselled that they will probably only notice a benefit after 2–4 weeks. Furthermore, when starting medication patients should be advised that there may be increased suicide ideation and risk of suicide in the first month. As such patients should be closely monitored for the first 4 weeks of a new medication.

Antidepressant medicines act by increasing levels of various neurotransmitters in the synaptic spaces such as serotonin, adrenaline and dopamine.

Selective serotonin reuptake inhibitors (SSRIs) (e.g. sertraline, citalopram, fluoxetine)

 

The most prescribed drugs for depression and considered first line. Widely available and usually well tolerated they work by increasing serotonin in the synaptic spaces by preventing its reuptake.

Selective serotonin-noradrenaline reuptake inhibitors (SNRIs) (e.g. venlafaxine)

 

Similar to SSRIs but they prevent the reuptake of noradrenaline as well. Can treat a wider variety of symptoms, such as chronic pain but are often less tolerated than SSRIs. Often used second line.

Tricyclic antidepressants (TCAs) (e.g. amitriptyline, nortriptyline)

 

These drugs primarily inhibit the reuptake of sertraline and adrenaline. They also have small inhibitory effect on the reuptake of dopamine. They are less selective than SSRIs/SNRIs binding to much wider array of receptors. Therefore, it has more side effects. They also carry much higher risk of fatal overdose. However, they are still used in the case of treatment resistant depression if previous drugs have failed.

Serotonin modulators (e.g. vortioxetine, trazodone, vilazodone)

These simultaneously block the reuptake of serotonin and stimulate the serotonin receptors in the synapse.

Atypical tetracyclic antidepressants (e.g. mirtazapine)

Can also be used second line or as an augmenting agent if patients develop side effects to SSRIs.

Monoamine oxidase inhibitors (MAOIs) (e.g. phenelzine)

These inhibit the breakdown of various neurotransmitters such as serotonin, adrenaline, and dopamine. They tend to be prescribed by specialist in treatment resistant depression due to adverse effects and the need to follow strict diets when taking it.  Highly contraindicated for combination use with other antidepressants due to high chance of serotonin syndrome.

Other

These therapies involve the direct electrical stimulation of the brain. This stimulates the release of neurotransmitters and may help stimulate growth in the portions of the brain believed to shrink in severe depression. They may also work by modifying electrical activity in different parts of the brain. They are also useful as a way to avoid harmful medication interactions in patients who are pregnant or have other medical conditions.

Electroconvulsive therapy (ECT)

This is used in people with very severe depression or those for which medication has failed. It involves the brief electrical stimulation of the brain while the patient is under anaesthesia. Delivered as a curse of treatment usually twice a week for 3–8 weeks. It is considered a safe low risk procedure with most of the side effects transient. However, there can be some mild long term memory loss. Demonstrates the most efficacy of any treatment in severe depression.

Transcranial magnetic stimulation (TMS)

This uses electromagnetic induction to deliver electrical stimulation to parts of the brain. It is considered very safe and has demonstrated short term efficacy. In addition, the patient can remain awake during the procedure making it easier to deliver. A course of treatment is typically a session a day for 5 days a week for several weeks.

Implanted vagus nerve stimulation (VNS)

Originally developed for seizure control, this involves the implantation of a device which delivers electrical stimulation to the brain along the vagus nerve. Used in treatment resistant depression unless the patient has acute suicidality.

Major Depressive Disorder

This is an online resource, produced by StatPearls. It is intended for healthcare professionals.

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Generalised anxiety disorder (GAD)

GAD is one of the most commonly diagnosed mental health disorders and its symptoms and consequences put pressure on both general practice and emergency departments. It is generally defined as chronic, excessive worry lasting more than six months which is having a disruptive impact on a person’s life. GAD does not include anxiety that is part of another mental health disorder, a result of substance misuse or another health condition (e.g. hyperthyroidism). However, it often occurs in association with major depression. Its management involves a stepped approach including both pharmacological and psychological therapies.

Aetiology

It is not clear exactly what causes GAD and what processes in the brain have become disrupted. It appears to be multifactorial. It often follows past traumatic events, has a genetic component and is more common in those with long term health issues. As well as being caused by drug and alcohol misuse, it can also precipitate these problems. It can also be triggered by regular life stressors, like unemployment, relationship issues and work stress. Psychological management often tries to identify possible triggers.

 Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders defines 6 key symptoms of GAD of which three must be present for a diagnosis. These are restlessness or nervousness, easily fatigued, poor concentration, irritability, muscle tension and sleep disturbance. There are autonomic symptoms such as sweating, dizziness or light-headedness, palpitations and nausea.

Management

The first step should be patient education through leaflets and signposting to resources. The arrangement of active monitoring of symptoms should be set up. In the case of a comorbid disorder such as depression, the primary disorder should be managed first.

First line management involves various low intensity psychological interventions guided by patient preference. These are for patients with symptoms but only minor functional impairment. These include:

  • Individual non-facilitated or guided self-help. This is usually based on cognitive behavioural therapy principles (CBT) and should be attempted for at least 6 weeks.
  • Group therapy. This is also based on CBT sessions and consists of groups of up to twelve people supported by one therapist. This should also be attempted for 6 weeks.

Second line management (the starting point if the patient presents with marked functional impairment) includes:

  • High intensity psychological therapy such as individual CBT sessions, for 1 hour weekly lasting at least three months.
  • Pharmacological treatments are detailed in the table below. It is worth noting that psychotherapy and pharmacological therapy can be combined.

Pharmacological management in primary care

It is usually advised that treatments be tried for 3 months before assessing effectiveness but patients should be seen after 1 month to assess for adverse effects.

Selective serotonin reuptake inhibitors (escitalopram, paroxetine)

The most common first line treatment for GAD. These increase the concentration of serotonin at the synapses by preventing its reuptake by the neurons via the serotonin transporter in the presynaptic terminal. Thought to be beneficial to mood, emotion, and sleep. Two different ones may be tried. Escitalopram is the preferred drug in this class for GAD.

Selective serotonin-noradrenalin reuptake inhibitors (duloxetine, venlafaxine)

These increase both the serotonin and noradrenaline concentration in the synapses. Venlafaxine has been shown in trials to have a much greater benefit versus placebo.

Pregabalin

This is an anticonvulsant which has been shown to have beneficial effects on anxiety versus placebo. Thought to have calming effect on ‘over-excited’ presynaptic neurons. Can be used alone or as an augmenting agent with other drugs.

Tricyclic antidepressants

Traditionally used to treat GAD. However, have higher rate of adverse events than other agents listed. Imipramine and clomipramine are the preferred agents for anxiety. Caution should be used in patients with suicide ideation as potentially fatal in overdose.

Additional pharmacological management in secondary care

 These drugs tend to only be for patients who are being managed by a specialist.

Benzodiazepines (diazepam)

Useful both for GAD and panic disorders. Appears to have particularly beneficial effects on any autonomic symptoms. Tolerance and dependence are potential issues.

Second generation antipsychotics (quetiapine)

Traditionally used to treat psychotic disorders, at lower doses has been shown to be beneficial. However, there is an increased risk of discontinuation due to adverse effects. Not licensed for this use in many countries. Risk of elongated QTc.

 

Scenario: Management of a person with generalized anxiety disorder

This a guide from the UK's National Institute for Health and Care Excellence (NICE) that describes best practice in managing adult patients with generalized anxiety disorder.

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GAD is one of the most commonly diagnosed mental health disorders and its symptoms and consequences put pressure on both general practice and emergency departments. It is generally defined as chronic, excessive worry lasting more than six months which is having a disruptive impact on a person’s life. GAD does not include anxiety that is part of another mental health disorder, a result of substance misuse or another health condition (e.g. hyperthyroidism). However, it often occurs in association with major depression. Its management involves a stepped approach including both pharmacological and psychological therapies.

Aetiology

It is not clear exactly what causes GAD and what processes in the brain have become disrupted. It appears to be multifactorial. It often follows past traumatic events, has a genetic component and is more common in those with long term health issues. As well as being caused by drug and alcohol misuse, it can also precipitate these problems. It can also be triggered by regular life stressors, like unemployment, relationship issues and work stress. Psychological management often tries to identify possible triggers.

 Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders defines 6 key symptoms of GAD of which three must be present for a diagnosis. These are restlessness or nervousness, easily fatigued, poor concentration, irritability, muscle tension and sleep disturbance. There are autonomic symptoms such as sweating, dizziness or light-headedness, palpitations and nausea.

Management

The first step should be patient education through leaflets and signposting to resources. The arrangement of active monitoring of symptoms should be set up. In the case of a comorbid disorder such as depression, the primary disorder should be managed first.

First line management involves various low intensity psychological interventions guided by patient preference. These are for patients with symptoms but only minor functional impairment. These include:

  • Individual non-facilitated or guided self-help. This is usually based on cognitive behavioural therapy principles (CBT) and should be attempted for at least 6 weeks.
  • Group therapy. This is also based on CBT sessions and consists of groups of up to twelve people supported by one therapist. This should also be attempted for 6 weeks.

Second line management (the starting point if the patient presents with marked functional impairment) includes:

  • High intensity psychological therapy such as individual CBT sessions, for 1 hour weekly lasting at least three months.
  • Pharmacological treatments are detailed in the table below. It is worth noting that psychotherapy and pharmacological therapy can be combined.

Pharmacological management in primary care

It is usually advised that treatments be tried for 3 months before assessing effectiveness but patients should be seen after 1 month to assess for adverse effects.

Selective serotonin reuptake inhibitors (escitalopram, paroxetine)

The most common first line treatment for GAD. These increase the concentration of serotonin at the synapses by preventing its reuptake by the neurons via the serotonin transporter in the presynaptic terminal. Thought to be beneficial to mood, emotion, and sleep. Two different ones may be tried. Escitalopram is the preferred drug in this class for GAD.

Selective serotonin-noradrenalin reuptake inhibitors (duloxetine, venlafaxine)

These increase both the serotonin and noradrenaline concentration in the synapses. Venlafaxine has been shown in trials to have a much greater benefit versus placebo.

Pregabalin

This is an anticonvulsant which has been shown to have beneficial effects on anxiety versus placebo. Thought to have calming effect on ‘over-excited’ presynaptic neurons. Can be used alone or as an augmenting agent with other drugs.

Tricyclic antidepressants

Traditionally used to treat GAD. However, have higher rate of adverse events than other agents listed. Imipramine and clomipramine are the preferred agents for anxiety. Caution should be used in patients with suicide ideation as potentially fatal in overdose.

Additional pharmacological management in secondary care

 These drugs tend to only be for patients who are being managed by a specialist.

Benzodiazepines (diazepam)

Useful both for GAD and panic disorders. Appears to have particularly beneficial effects on any autonomic symptoms. Tolerance and dependence are potential issues.

Second generation antipsychotics (quetiapine)

Traditionally used to treat psychotic disorders, at lower doses has been shown to be beneficial. However, there is an increased risk of discontinuation due to adverse effects. Not licensed for this use in many countries. Risk of elongated QTc.

 

Treatment of anxiety disorders

This is a published article (from 2017) that summarizes best practice in the treatment of anxiety disorders, including generalized anxiety disorder.

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GAD is one of the most commonly diagnosed mental health disorders and its symptoms and consequences put pressure on both general practice and emergency departments. It is generally defined as chronic, excessive worry lasting more than six months which is having a disruptive impact on a person’s life. GAD does not include anxiety that is part of another mental health disorder, a result of substance misuse or another health condition (e.g. hyperthyroidism). However, it often occurs in association with major depression. Its management involves a stepped approach including both pharmacological and psychological therapies.

Aetiology

It is not clear exactly what causes GAD and what processes in the brain have become disrupted. It appears to be multifactorial. It often follows past traumatic events, has a genetic component and is more common in those with long term health issues. As well as being caused by drug and alcohol misuse, it can also precipitate these problems. It can also be triggered by regular life stressors, like unemployment, relationship issues and work stress. Psychological management often tries to identify possible triggers.

 Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders defines 6 key symptoms of GAD of which three must be present for a diagnosis. These are restlessness or nervousness, easily fatigued, poor concentration, irritability, muscle tension and sleep disturbance. There are autonomic symptoms such as sweating, dizziness or light-headedness, palpitations and nausea.

Management

The first step should be patient education through leaflets and signposting to resources. The arrangement of active monitoring of symptoms should be set up. In the case of a comorbid disorder such as depression, the primary disorder should be managed first.

First line management involves various low intensity psychological interventions guided by patient preference. These are for patients with symptoms but only minor functional impairment. These include:

  • Individual non-facilitated or guided self-help. This is usually based on cognitive behavioural therapy principles (CBT) and should be attempted for at least 6 weeks.
  • Group therapy. This is also based on CBT sessions and consists of groups of up to twelve people supported by one therapist. This should also be attempted for 6 weeks.

Second line management (the starting point if the patient presents with marked functional impairment) includes:

  • High intensity psychological therapy such as individual CBT sessions, for 1 hour weekly lasting at least three months.
  • Pharmacological treatments are detailed in the table below. It is worth noting that psychotherapy and pharmacological therapy can be combined.

Pharmacological management in primary care

It is usually advised that treatments be tried for 3 months before assessing effectiveness but patients should be seen after 1 month to assess for adverse effects.

Selective serotonin reuptake inhibitors (escitalopram, paroxetine)

The most common first line treatment for GAD. These increase the concentration of serotonin at the synapses by preventing its reuptake by the neurons via the serotonin transporter in the presynaptic terminal. Thought to be beneficial to mood, emotion, and sleep. Two different ones may be tried. Escitalopram is the preferred drug in this class for GAD.

Selective serotonin-noradrenalin reuptake inhibitors (duloxetine, venlafaxine)

These increase both the serotonin and noradrenaline concentration in the synapses. Venlafaxine has been shown in trials to have a much greater benefit versus placebo.

Pregabalin

This is an anticonvulsant which has been shown to have beneficial effects on anxiety versus placebo. Thought to have calming effect on ‘over-excited’ presynaptic neurons. Can be used alone or as an augmenting agent with other drugs.

Tricyclic antidepressants

Traditionally used to treat GAD. However, have higher rate of adverse events than other agents listed. Imipramine and clomipramine are the preferred agents for anxiety. Caution should be used in patients with suicide ideation as potentially fatal in overdose.

Additional pharmacological management in secondary care

 These drugs tend to only be for patients who are being managed by a specialist.

Benzodiazepines (diazepam)

Useful both for GAD and panic disorders. Appears to have particularly beneficial effects on any autonomic symptoms. Tolerance and dependence are potential issues.

Second generation antipsychotics (quetiapine)

Traditionally used to treat psychotic disorders, at lower doses has been shown to be beneficial. However, there is an increased risk of discontinuation due to adverse effects. Not licensed for this use in many countries. Risk of elongated QTc.

 

Generalised anxiety disorder (BMJ Best Practice)

This is an online resource, produced by the British Medical Journal, that is intended for use by healthcare professionals.

No votes yet

Schizophrenia

Schizophrenia is a chronic brain disorder characterised by hallucinations, delusions, formal thought and movement disorders, behavioural changes and a lack of motivation. Symptoms are traditionally divided into positive and negative. The diagnosis is made clinically after a full psychiatric history and other causes of psychosis are excluded. The pathophysiology and causes of schizophrenia are multifaceted and extremely complex and there is no full understanding why it occurs. It has a relatively low prevalence affecting less than 1% of people in their lives. However, the burden of disease is high, and it is associated with high comorbidity (e.g. substance misuse). Primary management of schizophrenia is pharmacological, however keeping patients adherent to their medications is a challenge.

Aetiology

Schizophrenia is thought to be caused by an imbalance in multiple neurotransmitters, including serotonin, glutamine, dopamine and GABA signalling pathways. Risk factors can be genetic, environmental and social. The disorder seems to have a strong genetic inheritance with a 40% risk for the children of two people diagnosed with schizophrenia. There are multiple environmental factors including cannabis use and urbanisation, as well as pregnancy and birthing complications. These include pre-eclampsia, gestational diabetes, maternal malnutrition and winter births. Social risk factors include childhood trauma and social isolation.

Diagnosis

The DSM-5 says schizophrenia can only be diagnosed after a full psychiatric history and other causes of psychosis have been excluded. In order to make the diagnosis the patient must have two or more of the listed symptoms lasting at least one month. These are:

  • Delusions
  • Hallucinations
  • Disorganised speech
  • Grossly disorganised or catatonic behaviour
  • Negative symptoms e.g., anhedonia or a lack of motivation

It is important to take a full neurological, drug and social history as well as there are many other causes of psychosis. These are listed in the table below

Organic causes

Drug induced

Other psychiatric

Dementia

Parkinson’s disease

Multiple sclerosis

Syphilis

AIDS

Encephalitis

Heavy metal toxicity

Stroke

Brain tumours

Delirium

Metabolic disorders

Endocrine disorders

Corticosteroids

SSRI

Stimulants (Amphetamine)

Antihistamines

Anticonvulsants

Psychedelic drugs

Cannabis

Anti Parkinson’s drugs

Cardiovascular drugs

Alcohol withdrawal

Opiate withdrawal

 

Psychotic depression

Bipolar disorder

Delusional disorder

Paranoid personality disorder

Schizotypal personality disorder

Sleep related disorders.

Substance misuse

Schizoaffective disorder

 

Management

Management of schizophrenia involves a combination of approaches with symptom control being achieved using antipsychotics and social interventions once symptom control has been achieved.

Pharmacological

Second generation anti-psychotics are used first-line in the acute phase and include:

These are used first-line in preference to first generation anti-psychotics because of their better side-effect profiles and a higher rate of medication adherence. However, they can still be used either first or second line. Examples of first generation anti-psychotics include:

In treatment-resistant of schizophrenia, where two different antipsychotics have been unsuccessfully trialled, clozapine is used. This requires regular blood tests as there is a high risk of agranulocytosis.

Once the acute phase is managed patients are moved to the maintenance phase of management. This includes establishing a minimum effective dose to prevent relapse of the anti-psychotic used to control their symptoms in the acute phase. The maintenance dose can be given orally however a depot injection is usually preferred as it has significantly better rates of medication concordance.

There should also be management of any comorbid conditions. Substance misuse can significantly worsen symptoms so must be managed. Antidepressant and anxiolytics can be used to manage any persistent depressive or anxiety related symptoms.

Psychosocial

Social interventions have a significant role to play in prophylaxis. Rehabilitation into the community is very important as social isolation can worsen the disease. This includes participation of family in the healing process. This has been shown to improve disease outcomes and lower family distress. This can be combined with social skills training has been shown to help giving patients the skills to better communicate and interact with others. Common therapies employed are:

  • Family psychoeducation
  • Social skills training
  • Cognitive training
  • Cognitive behavioural therapy

Schizophrenia

This webpage covering schizophrenia is maintained by the healthcare education and technology company StatPearls. It can be accessed via the NCBI Bookshelf, which is a service of the National Library of Medicine and National Institutes of Health. The webpage was last updated in March 2023. It is suitable for healthcare professionals.

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