The main findings of this study can be summarized as (i) approximately 4 in 10 of the homicides committed by people with a psychotic illness occur before treatment, (ii) approximately 1 in 700 people with psychosis commit a homicide before treatment, (iii) approximately 1 in 10

000 patients with psychosis who have received treatment will commit a homicide each year, and (iv) the rate of homicide in psychosis before treatment is approximately 15 times higher than the annual rate after treatment.
In view of the implications of the findings for mental health services, we considered the limitations of the study and whether the findings are consistent with other studies of violence in psychosis. We also considered possible reasons for the lower rate of homicide in those who have received treatment.
Methodological Limitations
The first methodological limitation is that the studies relied upon elements of legal proceedings to establish the diagnosis of psychosis. Legal proceedings might not be a sensitive method of diagnosing psychosis
6 and might have biased the study toward finding fewer cases of homicide in first-episode psychosis because early or previously unknown psychosis might be less likely to come to the attention of the courts. In addition, the use of legal definitions of criminal responsibility in 4 studies probably excluded some offenders with psychotic illness who committed homicides for reasons other than their illness. The legal definitions were different in each of these 4 studies. Two studies included those found not guilty by reason of insanity according to local definitions,
14,18 and 2 used legal tests for any mental illness defense, even if the offender entered a plea of guilty to manslaughter.
3,17 Differences in the legal tests might not have greatly increased the heterogeneity in the proportion of homicide offenders in first-episode psychosis because the 2 studies with the higher threshold of not guilty by reason of insanity had high
14 and low
18 proportions of homicide in first-episode psychosis. Our study, which had a low legal threshold of the availability of a mental illness defense, included all but a very small percentage of the homicide offenders with psychotic illness and reported the highest homicide proportion of offenders in first-episode psychosis. This finding could in part be due to the inclusion of 8 of 54 first-episode homicide offenders with a diagnosis of affective psychosis or psychosis arising from substance abuse.
3The reliance on legal findings of psychosis probably has the advantage of other insensitive tests, in that it is likely to be specific. When a mental illness defense is raised in court, the accused is usually examined by more than one psychiatrist, and a legal finding of reduced criminal responsibility would be unusual without evidence of preexisting illness or disability. For this reason, it is unlikely that many of those included in the studies were misdiagnosed, malingering, or did not actually commit a homicide.
The second methodological limitation was that the total homicide rate was not available for each region. Although it has been asserted that rates of homicides by the mentally ill are unrelated to total homicide rates,
7 studies with a high total homicide rate often report a higher rate of homicide by the mentally ill.
9 The accuracy of the calculated rates for both the first episode of psychosis and previously treated psychosis might have been reduced because the true rate of homicide in psychosis might be higher in regions with high total homicide rates. This limitation is relevant because we were able to locate 1 study from the United States, where total homicide rates are several times higher than in most other developed countries.
The first 2 methodological limitations might affect the estimates of the number of homicides during psychosis (the numerator), whereas a third limitation relates to the assumptions about the number of patients with psychosis who do not commit a homicide (the denominator). While the study relied on the best available pooled estimates of the incidence and prevalence of psychosis, it is possible that some of the heterogeneity in the homicide rates resulted from variation in the actual incidence and prevalence of psychosis. For example, some regions might have had fewer homicides by people with psychosis because psychosis was less common.
Factors such as legal tests, the total homicide rate, and the uncertainty about the incidence and prevalence of psychosis add to the uncertainty of the calculated rates and CIs. However, these factors are less likely to have altered the proportion of homicide offenders in first-episode psychosis or the rate ratio of homicide in first-episode and previously treated psychosis. Sociological factors such as drug and firearm use that are associated with total homicide rates and the legal tests used to find cases are likely to have a similar effect on the number of homicides before and after treatment. Moreover, areas with a higher incidence of psychosis are also likely to have a higher prevalence of psychosis. Hence, estimates of the rate ratios are likely to be insensitive to the total homicide rate, legal tests, and variation in the incidence and prevalence of schizophrenia because all these factors can be expected to have a similar effect on the number of treated and untreated patients.
An exception would be if the incidence of psychosis is higher and the prevalence lower than generally accepted. However, even with unlikely assumptions about the incidence and prevalence of psychosis, the increased rate of homicide before treatment is still apparent. For example, if it is assumed that the incidence of first-episode psychosis is 40 per 100

000 per year (a figure that has been reported in less than 5% of incidence studies
32) and the prevalence is 250 per 100

000 (a figure that is lower than all but about 20% of prevalence studies
32), the rate ratio of homicide in first-episode psychosis is still 4 times greater than the annual rate after treatment.
Other limitations do not directly relate to uncertainty in the calculation of rates but do warrant consideration. The review relied on a small number of studies, which raises the possibility that the studies that found a higher number of homicides in first-episode psychosis were more likely to be published. However, publication bias is unlikely to have been a major factor because the history of treatment prior to the homicide was a main focus of 3 articles and personal communication with authors of studies who did not report the history of treatment before the homicide did not locate additional data. Moreover, there were no studies that did not show an increased rate of homicide in first-episode psychosis.
Another limitation was that most of the studies excluded patients who were thought to have forms of psychosis other than schizophrenia. Hence, the finding of this study might not be generalized to other forms of psychosis.
A final and potentially important limitation is that we assumed that the rate of homicide was constant over the course of later illness after initial treatment. However, the annual rate of homicide probably declines further because in our study 8 of the 34 (24%) homicides by previously treated patients occurred within 1 year of initial treatment.
3 Hence, the true rate of homicide in patients with well-established treatment could be lower than our estimate.
Is This Finding Consistent With Studies of Non-lethal Violence?
The risk of violence in the first episode of psychosis has recently been highlighted.
34–36 Studies of violence and mental disorder have generally only considered violence by patients following discharge from hospital or have not distinguished between treated and untreated patients.
37–39 However, the findings of this study are consistent with other studies that report serious violence in first-episode psychosis. First, the 6 studies of homicide in psychosis that were excluded because homicide rates could not be calculated had a pooled proportion of first-episode homicide offenders of 40.8% (119 of 292).
19–24 Second, 3 studies that were excluded because they included patients who committed nonlethal assaults reported that 30%, 48%, and 56% had never received treatment.
40–42 Third, case linkage studies of violent offenses and psychiatric treatment show that a high proportion of the violence by mentally ill people occurs before treatment. A Danish case register study reported that 24.9% of violent offenses committed by psychotic men occurred after treatment,
43 and an Australian case register study also found that the rate of conviction for violent offenses by schizophrenic patients is greatest in the years immediately prior to initial treatment.
44,45Finally, in a study that was prompted by the observation of numerous homicides in first-episode psychosis, we investigated whether major self-mutilation, another rare, violent and catastrophic complication of psychosis, is also more common prior to treatment. An examination of all the case reports published since 1960 of people who had removed an eye or a testicle or had severed a limb or their penis found that 143 of 189 had clearly documented psychotic illness and that 119 of the 143 (83.2%) were diagnosed with a schizophrenia-spectrum psychosis. Of the 119, treatment status could be ascertained in 101 cases and 54 (53.5%, 95% CI

=

43.7%–63.2%) had never received treatment.
46 We estimated the risk of major self-mutilation prior to initial treatment to be 25 times greater than the annual risk after treatment. Moreover, the delusions associated with this extreme type of deliberate self-injury were similar to those reported in many cases of psychotically motivated homicide, in that the patients generally believed that their life was threatened, although by their own body part rather than another person.
Possible Explanations
Further research is needed to establish why the rate of homicide is higher in first-episode psychosis. A possible explanation is that there are more people with untreated psychotic symptoms or milder forms of the illness in the community than has previously been recognized.
47 However, we believe this to be unlikely because programs designed to find untreated patients detect only a small number of additional cases.
48,49 Moreover, the cumulative distribution of treatment delay after the onset of psychosis in the published studies of duration of untreated psychosis shows that few patients present for treatment after 5 years, which suggests that few patients with the syndrome of schizophrenia never receive treatment.
4Another possibility is that people in the first episode of psychosis are more likely to commit homicide because they are younger, and younger people are known to be more prone to violence. However, the 2 studies that reported the age of the first-episode homicide offenders
2,3 both reported a mean age over 30 years, which is older than the mean age of presentation in most studies of psychosis
4 and is older than most nonpsychotic homicide offenders.
Other possible explanations for the decline in homicide after treatment include that dangerous patients who do not commit a homicide in their first episode might receive more intensive treatment, preventing further violence. It might also be that patients who experience a remission after treatment or receive an explanation for their symptoms retain sufficient insight to prevent them from committing a later homicide. Patients in the first episode of psychosis might have a pattern of positive symptoms that is associated with violence or that negative symptoms later in the illness reduces the incidence of violence. It is even conceivable that a period of treatment with antipsychotic medication has an enduring neurobiological effect that reduces the likelihood of extreme violence.