Description of the condition
Adjustment disorder (AD) is defined as an abnormal reaction that occurs in response to a stressful event, such as work-related problems, marital difficulties, familial problems and a range of other stressors, either acute or long term (Despland 1995). AD is distinguished from normal adaptive reactions to stressful events by the severity of symptoms or the impairment in functioning, or both. In psychiatry it is recognised that life events often have a role in triggering a range of illnesses such as major depressive disorder (MDD) but their presence is not essential, unlike in AD, where the diagnosis is contingent upon the presence of an identifiable and recent stressor. Psychiatric disorders are defined using two international systems of classification. The International Classification of Diseases 10th edition (ICD-10) (WHO 1992) is the World Health Organization compendium and the Diagnostic and Statistical Manual 4th edition (DSM-IV) is the American Psychiatric Association equivalent (APA 1994). Both recognise AD although there are some minor differences between the terminology and criteria used in each.
The symptoms of AD are similar to those of MDD and generalised anxiety disorder (GAD); therefore, distinguishing AD from other syndromes is difficult (Casey 2006). As well as symptoms, there may also be disturbance in functioning and sometimes this may be the dominant feature. ICD-10 requires the presence of both symptoms and impaired functioning before a diagnosis can be made, while DSM-IV specifies that one or the other may be present.
Several subtypes of AD are described in both DSM-IV and ICD-10, based on the dominant symptom patterns or the behaviour exhibited. These consist broadly of AD with depression, AD with anxiety, AD with disturbance of conduct and AD with mixed states (WHO 1992; APA 1994). AD may be acute (less than one month in ICD-10 or less than six months in DSM-IV) or chronic (more than one month but less than two years in ICD-10 or more than six months in DSM-IV). It is a self limiting condition and the prognosis is excellent with complete symptomatic and functional resolution being common unless there are persistent stressors. Even among those with AD who require psychiatric admission there are significantly fewer readmissions than among those with GAD, MDD or dysthymia/sub-threshold depression (Jones 2002), and less frequent use of outpatient and psychotherapeutic services (Bronisch 1991).
In certain groups of people AD is common. Among those who deliberately self harm (intentional self injury or self poisoning irrespective of the underlying NICE definition motivation) (NICE 2004), AD is the most common clinical diagnosis (Taggart 2006). It is also prominent in consultation-liaison psychiatry, being diagnosed in about 12% of psychiatric referrals in general hospitals (Strain 1998; Huyse 2001). Among acutely ill medical inpatients (Silverstone 1996) and in obstetric/gynaecology consultation-liaison (Rigatelli 2002) it is more common than other mood disorders including MDD. In a palliative care setting a recent meta-analysis found that the prevalence of AD was 15.4% and only marginally less than that for major depression (16.5%), while in oncological settings AD was more common than major depression (19.4% versus 14.9%) (Mitchell 2011). In primary care there are few studies but a prevalence range from 1% to 18% of consulters (Casey 1984; Blacker 1988) has been described, while a recent study identified AD in 2.4% of primary care consulters with emotional problems (Fernandez 2012). Within the psychiatric services, AD was identified in 11% to 36% of new outpatient referrals, depending on the assessment method (Shear 2000), and in around 9% of consecutive admissions to a public sector psychiatric unit (Koran 2002). The public health implications of AD are unclear since the data suggest that it is an uncommon disorder in the general population, being identified in only around 1% of the population (Ayuso-Mateos 2001). Internationally, the focus of service provision has been based on the very high prevalence of MDD as a major cause of disease burden (Ustün 2004). This has led to the establishment of guidelines for the treatment of depression (NICE 2009) in primary and secondary care including both pharmacological and psychological treatments. However, if it is further shown (as some studies have done) that AD might be the more appropriate diagnosis in many, due to conflation of the two conditions (Casey 2006), this could have major implications for the type and duration of treatment that is offered, including whether any specific intervention other than general support is required for these self limiting conditions. Major cost implications would flow from this, with significant savings on the drugs budget.
There has been general neglect of AD in research (Casey 2001), in particular, the psychobiology of the condition has received little attention. The focus in the few studies that have examined this has been on the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol levels after dexamethasone suppression have shown different patterns in those with AD (with depressive features) in comparison to MDD (Lindqvist 2008). There have been no studies on the psychobiology of the other subcategories of AD. Thus, the treatment of AD is not at present underpinned by any biological parameters.
For a condition that is as common as AD, especially in general hospital psychiatry as well as in emergency settings involving self harming patients, it is crucial that treatment recommendations are based on firm evidence and that the risks and benefits of recommended interventions are carefully weighed.
Description of the intervention
The importance of AD is that it requires only limited treatment due to its tendency to be short lived and to resolve spontaneously (Strain 2008). Pharmacological agents such as benzodiazepines and hypnotics are recommended for symptomatic relief of anxiety and insomnia in AD (Uhlenhuth 1995; Shaner 2000). Others recommend the use of alternative agents such as valerian and kava-kava since these are sometimes used in the treatment of GAD in preference to anxiolytics because of their non-addictive properties (Volz 1997). However, herbal remedies will not be included in the present review as per Cochrane policy. The role of antidepressive agents is much less clear in AD but one investigator (Stewart 1992) recommends their use in the treatment of minor depression, a term that is often used interchangeably, albeit inaccurately, with AD. A retrospective case note study (Hameed 2005) found that AD with depression showed a better response to antidepressants than did MDD. No particular group of antidepressants has been shown to be more effective than any other. Recommendations for the use of pharmacological agents in AD are not accompanied by any guidance on dosage or duration of treatment. Neither has there been any discussion on which antidepressive agents might be helpful in the treatment of AD with depression, an important consideration in light of its spontaneous and, usually, rapid resolution and the delay in onset of effect of antidepressants. On the other hand there have been recommendations that the focus should be on psychological therapies (Strain 2008) such as "mirror therapy", a form of holistic intervention used in those with AD post myocardial infarct (Gonzáles-Jaimes 2003), cognitive therapy for those who have AD associated with occupational dysfunction (van der Klink 2003), "ego-enhancing" therapy for older adults (Frankel 2001) and general support (De Leo 1989). The recommendations for pharmacotherapy are based on the opinions of individuals rather than on any examination of the evidence base for these interventions.
How the intervention might work
The psychobiology of AD has received scant attention. Therefore, the biological rationale for using pharmacological agents is unclear, apart from the pragmatic approach to prescribing for symptomatic relief irrespective of the underlying psychobiology of the illness. This assumes that the pathophysiology of subsyndromal conditions such as AD and full syndromes such as MDD and GAD are the same and that the response to treatment will therefore be the same. This view was reinforced by a recent systematic review that found antidepressants to be effective in depression (MDD, AD and dysthymia) with physical illness (Rayner 2010).
In the treatment of MDD, antidepressants are believed to act by enhancing the activity of monoamines (serotonin, adrenaline and dopamine) in the central nervous system and this might be one possible mechanism by which this occurs in AD. A possible impact on the HPA axis, thought to be involved in stress reactions and in MDD (Pariante 2008), might also be a possibility although there is little firm evidence in the literature to support this in the case of AD.
Another view on the psychobiology of AD is that it is a stress reaction similar to acute stress reaction and post-traumatic stress disorder (PTSD) (Maercker 2008). Following from this, it is arguable that broadly similar conditions such as AD might benefit from similar treatments that include the selective serotonin reuptake inhibitors (SSRIs), as these have been shown to be efficacious in this condition in a heterogeneous group of traumas of varying duration and severity (Stein 2006). Their efficacy is thought to result from their impact in controlling the dysregulation of the neurotransmitter systems and neuroendocrine systems (HPA axis), some of which may also be abnormal in AD.
With regard to benzodiazepines in AD with anxiety disorders, it is likely that they will work in a manner similar to that in GAD, by enhancing the action of gamma-amino-butyric acid (GABA) although the role of GABA has not been studied in the AD with anxiety subtype.
Why it is important to do this review
Recommendations for pharmacological treatments for AD have been developed by expert opinion rather than as a result of randomised controlled trials. Since it is a self limiting disorder, the treatment recommendations are for brief interventions with an emphasis on psychological therapies (Strain 2008) although there may be a role for the symptomatic treatment of insomnia and anxiety symptoms with hypnotics or tranquillizers (Uhlenhuth 1995; Shaner 2000).
Despite the limited evidence of the benefits of pharmacological treatments, in particular antidepressants, there are indications that antidepressants are increasingly being used in the treatment of AD (Diefenbacher 2002), due to what some authors describe as the "culture of prescribing" (Strain 2008). Recent data indicate that the condition which has shown the greatest increase in antidepressant usage is AD, with the rate of prescription changing from 22.26 per 100 cases in 1996 to 39.37 per 100 cases in 2005 (Olfson 2009). Therefore, it is important to consider the evidence, if any, for the use of pharmacological agents in general, and antidepressants in particular, in the treatment of AD. Since suicidal ideation and behaviour is common in those with AD (Kryzhanovskaya 2001), it is also of clinical relevance to identify whether pharmacological agents assist in reducing these.