When you do acute, crisis, community or inpatient psychiatry, you are using medications that in overdose can be risky. Moreover, you are working with people who have a tendency to overdose. So what you prescribe and how you prescribe matters. This paper, in the American Journal of Psychiatry has two important findings. The first is that the rate of intentional overdose is increasing.

It is worth nothing that the most recent trial of modified CBT in chronic depression did not allow participants to have medications: in previous trials the German group who did the study thought they were of limited utility.

But prescribe you will: you don’t want people to end up with chronic depression, and the combination of medication and CBT is probably as effective a treatment as is available. But what you prescribe… matters.

During the 15-year study period, there were 962,222 single substance exposures to the 48 medications. Mean age of the cases was 35.8 years; 62.8% were female. Suspected suicide was the reason recorded for 51.4% of all exposures, for 66.9% of exposures with serious outcomes, and for 74.1% of exposures with fatal outcomes. Other reasons for exposures with a frequency ?1% were therapeutic error (20.4%), unintentional general (6.5%), intentional misuse (5.8%), adverse reaction (5.4%), intentional abuse (3.8%), intentional unknown (3.1%), and unknown reason (1.6%). Oral ingestion of the medications accounted for 98.9% of the exposures. The number of serious outcomes (fatal, major, and moderate) increased 2.26-fold in linear fashion (R2=0.989, p<0.0001) during the 2000–2014 period (Figure 1A). The increase in exposures with less serious outcomes was lower, 1.31-fold, and more variable year to year (Figure 1B). During this period, fatal exposures increased 1.32-fold.

The second, and more useful thing this paper does, is not what happens in overdose. How people get sick, and what the risk is. The MAOIs are not used much, nor is Lithium, because of risk. But the risk of atypical antipsychotics, as with anticonvulsants, is higher than was initially thought.

Relative to other compounds, tricyclic antidepressants were associated with higher rates of acidosis, cardiac conduction problems, respiratory depression, and seizures. The number of exposures to monoamine oxidase inhibitors (MAOIs) was relatively low, but high rates of hypertension, confusion, increased creatinine, and fever were observed. Relative to other compounds, lithium was associated with higher rates of bradycardia, confusion, and renal problems such as elevated creatinine, oliguria, polyuria, and renal failure.

Bupropion had the highest rate of single and multiple seizures and the highest rate of hallucinations among second-generation antidepressants. Venlafaxine was associated with conduction disturbance, tachycardia, and single seizures, but the rates for these events were not unusually high compared with other medications, and they did not explain the higher mortality index. Citalopram was associated with higher rates of conduction disturbance, seizures (single and multiple), acidosis, and electrolyte disturbances among the SSRIs.

Quetiapine and olanzapine had relatively high rates of coma and respiratory depression relative to other medications. Olanzapine and ziprasidone had relatively elevated rates of conduction disturbance and ECG changes. Valproic acid had relatively high levels of acidosis and coma. As a group, the anticonvulsants had high rates of electrolyte abnormalities, with lamotrigine and oxcarbazepine having the highest. Carbamazepine had high rates of coma and the highest rate of nystagmus of any drug. Lamotrigine had the highest rate (2.1%) of skin rash of any drug.

Among other compounds used to treat anxiety in depression, buspirone had a high rate of bradycardia similar to trazodone, nefazodone, and lithium. Benzodiazepines and pregabalin had moderately high rates of coma and elevated rates of respiratory depression. The morbidity indices for the two combination products, olanzapine/fluoxetine and perphenazine/amitriptyline, were similar to those for olanzapine and amitriptyline, respectively.

We do not have the combination products available in NZ. They are available in the USA. One of the advantages of having a drug purchasing monopoly in NZ is that we lag behind other countries, and this allows us to avoid some products.

The CDC has done us a service by giving us the figures for the USA. If CBT is not working, I consider the risk profile when I reach for the prescription pad.