Test of Treatment in Psychiatric Practice

Abstract

Due to lack of laboratorial investigations in psychiatric practice, tests of treatment are often used to aid diagnosis. This article provides examples of test of treatment in psychiatric practice and outlines their limitations.

Test of Treatment

Test of treatment refers to the practice of using response to certain treatment as a diagnostic tool.¹ For example, using reversibility of airway obstruction after administering a short acting bronchodilator to diagnose asthma.² Another example is the use of short acting anticholinesterase such as edrophonium to diagnose Myasthenia Gravis (MG).³ In this case, increased muscle strength in such patient indicates the presence of MG. However, lack of response to treatment or re-emergence of symptoms upon withdrawing treatment may point to a different diagnosis or confirm initial diagnosis respectively. Test of treatment is commonly used in clinical practice but it has several pitfalls.¹ In psychiatric practice, due to lack of laboratorial investigations to aid diagnosis, it becomes necessary in some cases to use the test of treatment. There are several factors that limit the sensitivity and specificity of this test in psychiatric disorders.

Factors That Reduce Sensitivity (Increasing False Positives)

• A) Psychiatric disorders have high placebo response rates.^4-6

• B) The increased incidence of spontaneous remission in psychiatric disorders. A meta analysis of depression studies using waiting list control groups found that 20% of depressed patients improved to a degree comparable to what would be considered a positive response to antidepressant treatment.⁷ Furthermore, a good outcome observed with intervening early in the course of psychosis-including the use of antipsychotic medication-maybe explained by the tendency of patients with psychosis of recent onset to remit spontaneously, rather than a direct result of the intervention.⁸

• C) Lack of treatment specificity of psychiatric drugs. Antidepressants are used to treat depression but can be used in a variety of psychiatric conditions such as generalised anxiety disorder, obsessive compulsive disorder, panic disorder, post traumatic stress disorder, social phobia, premenstrual dysphoric disorder and borderline personality disorder. They even could be useful in obesity, smoking cessation and alcoholism.⁹ Similarly, a number of antipsychotic drugs have been indicated in treatment of schizophrenia, mania and more recently bipolar depression.¹⁰ Antipsychotic drugs may also have some role in treating non-psychotic disorders.¹¹

Factors That Reduce Specificity (Increasing False Negatives)

The use of inadequate dose or inadequate duration of treatment.¹ A number of studies have shown that psychiatric disorders such as depression and anxiety are often undertreated.^12,13

Examples of Using the Test of Treatment in Psychiatric practice

Mood disorders: A trial of antidepressant treatment could be given when an atypical presentation of depression is suspected. Depression can present with aggression and challenging behaviour in patients with severe learning disability.¹⁴ In elderly patients, depression could present as pseudodementia or behavioural challenges such as refusing food, incontinence, screaming, falls and violent behaviour.¹⁵ Intravenous diazepam test (DT) has been used to distinguish primary depression from depression secondary to anxiety. DT could also predict future response to treatment with either antidepressants or anxiolytics.¹⁶ On the other hand, lack of response to antidepressant treatment in depressed patients should point to the possibility of an alternative diagnosis such as bipolar affective disorder.¹⁷

Psychosis: Re-emergence of psychotic symptoms on withdrawal of antipsychotic treatment may be considered a relapse and confirm the presence of a suspected psychotic disorder. However, these symptoms may represent a rebound reaction to discontinuation of medication and have been reported even in people without previous psychiatric history.¹⁸ In alcoholic patients with recent onset psychotic symptoms, if delirium tremens is suspected, a course of benzodiazepine maybe given. Subsequent resolution of psychotic symptoms may confirm diagnosis of delirium tremens. However, benzodiazepines have also been found to alleviate psychotic symptoms that are not related to alcohol withdrawal¹⁹ (reducing sensitivity of the test). Lack of response to at least two antipsychotic drugs used sequentially in adequate doses and for 6–8 weeks each, leads to a diagnosis of treatment resistant schizophrenia (TRS) for which clozapine is the only licensed treatment. Recent studies have shown that lack of response to an antipsychotic drug within the first two weeks of treatment strongly predicts late lack of response to the same drug.^20,21 This finding suggests that the decision to continue with the same antipsychotic medication or to switch to a different one could be made after 2 weeks of treatment. This would result in earlier identification and treatment of patients with TRS.

Conversion disorders: Symptoms of conversion disorder may quickly resolve in response to placebo administration.^22,23 However, the use of placebo in clinical practice faces ethical challenges²⁴ as well as the problem of the re-enforcement of the need of unnecessary treatment.²² On the other hand, malingered disorders may also respond quickly to placebo.²⁵ Intravenous injection of saline solution could successfully induce psychogenic non-epileptic seizures differentiating them from epileptic seizures.²⁶ The sensitivity of this test is reduced by the finding that 1 in 5 of true seizure patients also has psychogenic seizures.²⁷

Making clinical diagnosis is often a subconscious cognitive process. Practitioners who use the test of treatment in psychiatry are at risk of making diagnostic errors through a number of cognitive biases such as misinterpreting the outcome of the test, overemphasising positive outcomes or dismissing negative ones. Test of treatment has a role in psychiatric practice but practitioners should interpret its outcome with caution.