Seroxat: what the textbooks and datasheet say

Paroxetine (trade name Seroxat) is an antidepressant in the group known as serotonin specific reuptake inhibitors (SSRIs), the best known of which is fluoxetine (Prozac).

Paroxetine is licensed for the treatment of major depression, obsessive-compulsive disorder, panic disorder; social anxiety disorder; post-traumatic stress disorder; generalised anxiety disorder.

The British National Formulary (BNF) 52, September 2006, includes the following warnings for paroxetine:

• Extrapyramidal reactions (including orofacial dystonias) and withdrawal syndrome are reported to the CSM more commonly with paroxetine than with other SSRIs.
  
  [Extrapyramidal reactions are movement problems that resemble Parkinson’s disease. Orofacial dystonias are uncontrolled, involuntary movements of the muscles around the mouth. These side effects are more commonly associated with antipsychotic drugs and not generally with antidepressants.]
  
  
• CSM advice on dosage
  The recommended dose for the treatment of depression, social anxiety disorder, generalised anxiety disorder, and post-traumatic stress disorder is 20 mg daily and for obsessive-compulsive disorder and panic disorder it is 40 mg daily. There is no evidence that higher doses are more effective.

The following warnings apply to SSRI antidepressants as a group:

• Withdrawal
  Gastro-intestinal disturbances, headache, anxiety, dizziness, paraesthesia, sleep disturbances, fatigue, influenza-like symptoms, and sweating are the most common features of abrupt withdrawal of an SSRI or marked reduction of the dose; the dose should be tapered over a few weeks to avoid these effects.
• CSM advice (depressive illness in children and adolescents)
  The CSM has advised that the balance of risks and benefits for the treatment of depressive illness in individuals under 18 years is considered unfavourable for the SSRIs citalopram, escitalopram, paroxetine, and sertraline, and for mirtazapine and venlafaxine. Clinical trials have failed to show efficacy and have shown an increase in harmful outcomes. However, it is recognised that specialists may sometimes decide to use these drugs in response to individual clinical need; children and adolescents should be monitored carefully for suicidal behaviour, self-harm or hostility, particularly at the beginning of treatment.
  
  Only fluoxetine has been shown in clinical trials to be effective for treating depressive illness in children and adolescents. However, it is possible that, in common with the other SSRIs, it is associated with a small risk of self-harm and suicidal thoughts. Overall, the balance of risks and benefits for fluoxetine in the treatment of depressive illness in individuals under 18 years is considered favourable, but children and adolescents must be carefully monitored as above.

The following warning applies to all antidepressants as a group:

• Suicidal behaviour and antidepressant therapy
  The use of antidepressants has been linked with suicidal thoughts and behaviour. Where necessary patients should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the dose is changed.

Drug datasheet
The list of side effects on the paroxetine drug datasheet (produced by the drug company as the basis for the licence to market the drug) includes the following psychiatric effects:

• Common: somnolence, insomnia, agitation; Uncommon: confusion, hallucinations; Rare: manic reactions, anxiety, depersonalisation, panic attacks, akathisia (see below). These symptoms may also be due to the underlying disease.

The datasheet also includes the following special warnings and precautions for use:

• Use in Children and adolescents under 18 years of age
  Paroxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide related behaviours (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If based on clinical needs, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
• Suicide/suicidal ideation
  Depression is associated with an increased risk of suicidal thoughts, self harm and suicide. This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience with all antidepressant therapies that the risk of suicide may increase in the early stages of recovery.
  Other psychiatric conditions for which paroxetine is prescribed can also be associated with an increased risk of suicidal behaviour. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
  Patients with a history of suicidal behaviour or thoughts, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
  There is a possibility of an increased risk of suicide related behaviour in young adults ages 18-29.
  Young adults should therefore be monitored carefully throughout treatment.
  There are insufficient data concerning the risk of suicide related behaviour in treatment naïve patients, but careful monitoring might be warranted.
  Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present.
• Akathisia
  The use of paroxetine has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

The datasheet can be viewed at emc.medicines.org.uk You can type the name of the drug into the search box at the top right-hand corner of the page, and it will find the Patient Information Leaflet (PIL) and the Summary of Product Characteristics (SPC) which is detailed technical information.

Paroxetine is normally dispensed in the form of tablets, but it is also available as a liquid. This could be diluted, and may be used to help withdrawal, since successive dilutions can make withdrawal very gradual. A pharmacist may be able to advise on this.

If you are stopping taking medication it is advisable to reduce the dose gradually, as it is difficult to predict who will have problems withdrawing. It is worth getting as much information and support as you can, and involving your doctor wherever possible.