# 04 - Differential diagnosis of psychiatric adverse

# Differential diagnosis of psychiatric adverse effects

972
The Maudsley® Prescribing Guidelines in Psychiatry
CHAPTER 15
Differential diagnosis of psychiatric adverse effects
A wide range of confounding factors complicate the diagnosis (and perhaps also the 
recognition) of psychiatric adverse effects. For example, physical illness, co-­prescribed 
medication, non-­prescribed agents and pre-­existing mental illness may all influence the 
clinical presentation and outcome. Factors determining the probability of a causal relationship between drugs and psychiatric adverse effects are shown in Box 15.1. To further support clinical decision-­making, the Naranjo scale can be used to assess the 
likelihood of any adverse reaction being drug-­related (Table 15.4). Although cessation 
of the implicated non-­psychotropic might be indicated in some cases, such decisions 
require individual considerations beyond the scope of this book.
Table 15.3  (Continued )
Drug
Psychiatric adverse effect
Comment
Isotretinoin17
Depression, suicidal ideation, 
psychosis
Sporadic reports of psychiatric ADRs but a 
causal link between isotretinoin therapy and 
depression, anxiety, mood changes or suicidal 
ideation/suicide has not been established. A 
recent meta-­analysis found no 
epidemiological evidence to suggest an 
increased risk of suicide and psychiatric 
conditions with isotretinoin.18 Moreover, 
isotretinoin may be associated with a lower 
risk of suicide attempt following treatment.18 
Rare, idiosyncratic reactions cannot be ruled 
out; if they occur the drug should be 
discontinued. Risk is no higher in those with 
prior suicide attempts and is not dose-­ or 
treatment-­duration-­related.
Montelukast19
Sleep disorders, hallucinations, 
anxiety, depression, obsessive 
compulsive symptoms
The UK MHRA has issued warnings about 
neuropsychiatric reactions associated with 
montelukast. Reactions have been reported in 
adults, adolescents and children. Evidence is 
conflicting, with one systematic review 
identifying associations with anxiety and 
sleeping disorders but not suicide and 
depression-­related events.20
ACE, angiotensin-­converting enzyme; BPH, benign prostatic hyperplasia; COMT, catechol-­O-­methyltransferase; 5HT, 
5-­hydroxytryptamine; MAO-­B, monoamine oxidase B; MHRA, Medicines and Healthcare products Regulatory Agency; 
RCTs, randomised controlled trials.

Miscellany
CHAPTER 15
Box 15.1  Factors determining the probability of a causal relationship between drugs and 
psychiatric adverse effects4,21
■
■Temporal relationship between the drug exposure and the psychiatric adverse effect
■
■Evidence of the specific psychiatric adverse effect occurring with the suspected drug
■
■Plausible pharmacological mechanism for the psychiatric adverse effect (e.g. dopamine agonists 
and psychosis)
■
■Presence of alternative explanations for symptoms (e.g. pre-­existing mental illness, de novo 
­psychiatric illness, other drugs)
■
■Response of symptoms to the withdrawal of the drug
■
■Effect of rechallenge with the same drug
Table 15.4  Adapted Naranjo adverse drug reaction (ADR) probability scale criteria.22
Questions
Yes
No
NA/unknown
1. Are there previous conclusive reports on this reaction?
+1
0
2. Did the ADR appear after the suspected drug was administered?
+2
–1
3. Did the ADR improve when the drug was discontinued?
+1
0
4. Did the ADR appear with rechallenge?
+2
–1
5. Are there alternative causes for the ADR?
–1
+2
6. Did the reaction appear when placebo was given?
–1
+1
7. Was the drug detected in the blood at toxic levels?
+1
0
8. Was the ADR more severe when the dose was increased, or 
less severe when the dose was decreased?
+1
0
9. Did the patient have a similar reaction to the same or similar 
drugs in any previous exposure?
+1
0
10. Was the ADR confirmed by any objective evidence?
+1
0
Probability score: ≥9 = definite; 5–8 = probable; 1–4 = possible; ≤0 = doubtful.