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.

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.


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.
PregabalinThis 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 antidepressantsTraditionally 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.

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 causesDrug inducedOther 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

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