3.4. Adverse Events
The most frequently reported adverse events were nausea, shown in 2/14 (14.4%), throat irritation shown in 2/14 (14.4%), headache shown in 2/14 (14.4%), and dry cough shown in 4/14 (28.6%) (
Table 3).
Table 4 shows the distribution of the four most commonly reported adverse events (AEs), separately for failures, reducers, abstainers. These events were most commonly reported at the beginning of the study and appeared to wane spontaneously by study visit 5. Withdrawal symptoms were absent (
i.e., depression, anxiety, insomnia, irritability, hunger, constipation were not reported). Moreover, no serious adverse events (
i.e., events requiring unscheduled visit to the family practitioner or hospitalization) occurred during the study.
Table 3.
Adverse events reported by participants who completed all study visits.
Table 3.
Adverse events reported by participants who completed all study visits.
Adverse Event | Study Visits |
---|
4-week n/n (%) | 8-week n/n (%) | 12-week n/n (%) | 24-week n/n (%) | 52-week n/n (%) |
---|
Throat irritation * | 1/14 (7.2%) | 2/14 (14.4%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Mouth Irritation * | 0/14 (0%) | 0/14 (0) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Sore Throat | 0/14 (0%) | 0/14 (0) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Dry cough | 4/14 (28.6%) | 4/14 (28.6%) | 1/14 (7.2%) | 0/14 (0%) | 0/14 (0%) |
Dry mouth | 0/14 (0%) | 0/14 (0) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Mouth ulcers | 0/14 (0%) | 0/14 (2.9%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Dizziness § | 0/14 (0%) | 0/14 (0) | 0/14 (10%) | 0/14 (0%) | 0/14 (0%) |
Headache | 2/14 (14.4%) | 1/14 (7.2%) | 1/14 (7.2%) | 0/14 (0%) | 0/14 (0%) |
Nausea | 2/14 (14.4%) | 0/14 (0%) | 1/14 (7.2%) | 0/14 (0%) | 0/14 (0%) |
Depression | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Anxiety | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Insomnia | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Irritability | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Hunger | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Constipation | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) | 0/14 (0%) |
Table 4.
Distribution of the four most commonly reported adverse events (AEs), separately for failures, reducers, abstainers.
Table 4.
Distribution of the four most commonly reported adverse events (AEs), separately for failures, reducers, abstainers.
AEs | 4-week | 8-week | 12-week | 24-week | 52-week |
---|
Dry cough | failures (n 2) | failures (n 2) | failures (n 0) | failures (n 0) | failures (n 0) |
reducers (n 1) | reducers (n 1) | reducers (n 1) | reducers (n 0) | reducers (n 0) |
abstainers (n 1) | abstainers (n 1) | abstainers (n 0) | abstainers (n 0) | abstainers (n 0) |
Headache | failures (n 0) | failures (n 0) | failures (n 0) | failures (n 0) | failures (n 0) |
reducers (n 1) | reducers (n 0) | reducers (n 0) | reducers (n 0) | reducers (n 0) |
abstainers (n 1) | abstainers (n 1) | abstainers (n 1) | abstainers (n 0) | abstainers (n 0) |
Nausea | failures (n 1) | failures (n 0) | failures (n 0) | failures (n 0) | failures (n 0) |
reducers (n 0) | reducers (n 0) | reducers (n 0) | reducers (n 0) | reducers (n 0) |
abstainers (n 1) | abstainers (n 0) | abstainers (n 0) | abstainers (n 0) | abstainers (n 0) |
Throat irritation | failures (n 0) | failures (n 1) | failures (n 0) | failures (n 0) | failures (n 0) |
reducers (n 1) | reducers (n 1) | reducers (n 0) | reducers (n 0) | reducers (n 0) |
abstainers (n 0) | abstainers (n 0) | abstainers (n 0) | abstainers (n 0) | abstainers (n 0) |
3.6. Discussion
We have shown for the first time that the use of e-cigarettes substantially decreased cigarette consumption without causing significant side effects in chronic schizophrenic patients who smoke. This was achieved without negative impacts on symptoms of schizophrenia as assessed by SAPS and SANS symptoms scales.
Severity of nicotine dependence, smoking prevalence, and the likelihood of success of quit attempts are much worse in schizophrenia than in patients with other mental disorders or smokers in the general population. Therefore, our findings may be of great importance.
Smokers with schizophrenia may use nicotine as a self-medication for the illness. The self medication hypothesis is supported by study showing that smoking can transiently reverse the deficit [
6] in the processing of auditory stimuli that is found in patients with schizophrenia [
31] and by research suggesting that smoking cigarette has a beneficial effect on visuospatial working memory in smokers with schizophrenia [
32].
Patients with schizophrenia may also smoke to offset the side effects of antipsychotic drugs, as suggested by research showing that a nicotine patch attenuates the adverse side effects of these drugs [
33] and that cigarette smoking reduces neuroleptic-induced parkinsonism [
34].
Another hypothesis is that some antipsychotic drugs may increase smoking, as suggested by research showing that haloperidol caused a dose-related increase in
ad lib smoking in patients with schizophrenia, in comparison with their baseline level when they were taking no antipsychotic medications [
35].
A further hypothesis is that genetic factors explain the co-occurrence of smoking and schizophrenia [
36], as suggested by research showing that nicotinic receptors are abnormally expressed [
37] and function abnormally in people with schizophrenia [
38].
In this pilot study, we have shown for the first time that substantial and objective modifications in the smoking habits may occur in smokers with schizophrenia using e-cigarettes, with significant smoking reduction and smoking abstinence and no apparent increase in withdrawal symptoms and in positive and negative symptoms of schizophrenia. Chronic schizophrenic patients using e-cigarettes substantially decreased cigarette consumption with an overall quit rate in 2/14 (14.3%) at week-52. Moreover, at least 50% reduction in cigarette smoking was observed in 7/14 (50%) of participants. Overall, combined reduction and smoking abstinence was shown in 9/14 (64.3%) of participants. Some of the smoking/reduction failures could have been related to malfunctions and technical failures of the product tested in the present study.
These preliminary findings are of great importance considering that chronic schizophrenic patients who smoke are generally not interested in quitting. The large magnitude of this effect suggests the e-cigarette may be a valuable tool of tobacco harm reduction in this special population. These positive findings may be explained by the great compensatory effect of e-cigarettes at both physical and behavioral level [
9,
10,
11,
12,
13,
14]; in particular these products are known to provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures (e.g., hand-to-mouth action of smoking). In agreement with this, we have recently demonstrated that nicotine free inhalators can only improve quit rates in those smokers for whom handling and manipulation of their cigarette played an important role in their ritual of smoking [
39].
The most frequent adverse events reported by our patients were throat irritation, nausea, headaches and dry cough, but all appeared to wane spontaneously with time. Throat irritation and dry cough are likely to be secondary to exposure to propylene glycol mist generated by the e-cigarette’s atomizer. Propylene glycol is a low toxicity compound widely used as a food additive and in pharmaceutical preparations. Exposure to propylene glycol mist may occur from smoke generators in discotheques, theatres, and aviation emergency training and is known to cause ocular, mouth, throat, upper airway irritation and cough [
40,
41].
In contrast with other ENDDs that are known to generate substantial level of eCO [
42], in the present study, the smoking reduction/cessation with “Categoria” e-cigarette use was associated to a substantial decrease in the level of eCO. This is in agreement with previous studies [
17,
18].
Therefore, the e-cigarette can be seen as a safe harm-reduction strategies for smokers with schizophrenia. Harm-reduction strategies are aimed at reducing the adverse health effects of tobacco use in individuals unable or unwilling to quit. Substantially reducing the number of cig/day is one of several kinds of harm reduction strategies [
43]. Here, we propose an alternative harm reduction approach for patients with schizophrenia with the e-cigarette being used as a safe alternative source of nicotine for patients who smoke.
It is uncertain whether substantial smoking reduction in smokers using the e-cigarette will translate in health benefits, but a number of studies have analyzed the ability of smoking reduction to lower health risks and have reported some reductions in cardiovascular risk factors and lung cancer mortality [
44,
45,
46]. Moreover, reduction in cigarette smoking by e-cigarette may well increase motivation to quit as indicated by a substantial body of evidence showing that gradually cutting down smoking can increase subsequent smoking cessation among smokers [
47,
48,
49,
50].
There are some limitations in our study. Firstly, this was a small uncontrolled study, hence the results observed may be due to a chance finding and not to a true effect; consequently the results should be interpreted with caution. However, it would have been quite problematic to have a placebo arm in such a study. Secondly, this is not an ordinary cessation study and therefore direct comparison with other smoking cessation products cannot be made. Lastly, assessment of withdrawal symptoms in our study was not rigorous. Withdrawal was assessed at each visit by simply asking about the presence/absence of irritability, restlessness, difficulty concentrating, increased appetite/weight gain, depression or insomnia. It is likely that this way of collecting information is liable to recall bias. Therefore, the reported lack of withdrawal symptoms in the study participants should be considered with caution [
4].