Antidepressants medications and the relative risk of suicide attempt.

This study was conducted on patients (n=1283) of different ages, 924 males and 359 female. These patients were attended to poison unit at emergency hospital, Mansoura University during the period from January 2002 to December 2009. The aim of this study was to characterize patients on antidepressants after self-poisoning with suicidal intent regarding age, sex, type of current antidepressant therapy, and type of substances ingested in order to commit suicide. During the study period, 175 Para suicide patients were found with current antidepressants therapy and presented with self-poisoning using their antidepressant therapy or other medications. A substantial difference between different types of antidepressants was found. Para suicide risks for selective serotonin reuptake inhibitor were significantly low than those of tricyclic antidepressants, so in suicide prevention, risks and benefits of an antidepressant should be taken into account when choosing treatment for depressive patients. At the same time, depressed patients should be under close psychiatric assessment in order to prevent such possible suicidal attempts.

INTRODUCTION

Tricyclic antidepressants (TCAs) have been approved by the Food and Drug Administration (FDA) specifically to treat depression, with their generic or chemical names. The majority of studies focus on completed suicides, but it has to be emphasized that the epidemiology of Para suicide, as a suicide act not aiming at death but, primarily at drawing attention to the subject's desperate situation, is different from that of suicide. As most attempted suicides is nonviolent, generally involving self-poisoning. Knowledge of the type of substances that are frequently used in Para suicides can help the emergence physician to deal properly with patient.[1] Para suicide is the strongest risk factor for suicide; so, identifying risk factors for suicidal behavior that can be assessed and modified by therapeutic/preventive interventions is a major public health issue.[2] There is no regular population-based monitoring of epidemiological data regarding Para suicide, but it is estimated to be 10–25 times more frequent than completed suicide.

The strongest correlates of Para suicide relate to the subject's depressive state at around the time of the suicidal behavior.[3] The most frequent method of Para suicide is intentional drug overdose, defined as substance ingestion in excess of the prescribed or generally recognized therapeutic dosage.[4] Several studies have liked the use of antidepressants to increased risks of suicidal behavior. On February 2, 2004, FDA issued a report asking manufactures of antidepressant drugs to include warnings on their drug label about the need to monitor people taking antidepressants for worsening depression and the emergence of suicidal thoughts. During the last 10 years, several new antidepressants, including selective serotonin reuptake inhibitors (SSRIs), has been introduced in Egypt. While one of the major problems with TCAs is their toxicity in overdose,[5] the new antidepressants have been claimed to be effective as tricyclics[6] and less toxic.[27-9] However,[10] assed risks of various antidepressants by relating number of Para suicide to particular drugs; they found higher risks with SSRIs. Fluxetine represents the prototype of the SSRIs and has been in wide spread use for over a decade.[11] Therefore, the aim of this work is to uncover the correlation between continuous intake of antidepressants among depressed patients and tendency to commit suicide and to detect particular types of antidepressants associated with higher risk.

MATERIALS AND METHODS

Patients

The study included the entire patient on antidepressants therapy and presented with drug over dose in suicidal intent attending the poison unit in emergency hospital, Mansoura University during the period between January 2002 and December 2009, who satisfied the following criteria:

A diagnosis of self-poisoning by their antidepressant therapy or other drugs.

A diagnosis of current treatment with any of antidepressants.

A total number of 1283 patients (924 males and 359 female) of different ages and signs of TCAs poisoning, attended the poison unit. At the time of arrival to hospital, all of the patient were underwent clinical and toxicological evaluation.

History

In this study, data were collected from patients, relatives, friends, or paramedics as regards:

Age, sex.

Present history of treatment with one of antidepressants.

Type of current antidepressant therapy.

Duration of starting antidepressant therapy.

Clinical evaluation

Physical examinations for findings related to anticholinergic manifestations, CNS signs, and other possible drugs taken in suicidal attempts.

Laboratory investigations

Detection of drug abuse in blood samples by enzyme multiplying immune assay technique (EMIT):

Blood samples (3 ml) were obtained from all patients, centrifuged and TCA was measured by enzyme multiplying immunoassay technique (Vita lab viva analyzer, Germany) according to TCA assay method in the viva manual in poison laboratory at emergency hospital, Mansoura University. Serum TCA levels are not likely to be helpful in the immediate treatment of the patient with TCA poisoning.

Statistical analysis

The quantitative data were presented as mean ± standard deviation and the qualitative data were presented as number and percentage.

RESULTS

The annual number and percentage of positive cases of TCA by EMIT are shown in Table 1 according to the total number of samples. The age of patients ranged between 19 and 39 years with a mean age 23.52±6.09. To characterize patients, age groups were reported in intervals of 5 years (19–24, 25–29, 30–34, and 35–39). As regards sex, among those were 80 males (45.7%) and 95 females (54.3%) with a sex ratio 1:1.19, the distribution of Para suicides according to age and sex is shown in Table 2. A large variety of substances was used to commit suicide. The most common substance taken to commit suicide was the current antidepressants treatment (47.5% for males and 38.95% for females). Males were significantly more likely to take benzodiazepines than females (30% and 10.53%, respectively), whereas females were more likely to take organophosphorus than males (30.52% and 12.5%, respectively), Table 3.

Table 1

Annual number and percentage of positive cases of TCA according to the total number of samples

Table 2

Patients with positive antidepressants (n=175) by age and sex

Table 3

Different substances taken by para suicide patients

Among Para suicides patients (n=175), 63% of patients were treated by TCAs, while SSRIs were taken only by 27% of patients. Amitriptyline was the major drug responsible for Para suicide cases on TCA (25% of cases), then dothiepen (20%) and clomipramine (10%), while citalopram was the major drug responsible for Para suicide cases on SSRIs (11% of cases), then sertaline (7%) and fluoxetine (5%). Mixed TCA and SSRIs were taken only by 2% of cases. Some Para suicides were on antidepressants other than TCA or SSRIs, e.g., bupropion (norepinephrine and dopamine reuptake inhibitor), responsible only about 4% of cases, and trazodone (serotonin and norepinephrine reuptake inhibitor), it represented only 4% of cases. Different antidepressants used by the patients as a treatment during study period are shown in Table 4.

Table 4

Different antidepressants used by the patients as a treatment during study period

DISCUSSION

In this study, the incidence of cyclic antidepressant poisoning is higher in female than in male. This most likely reflects a higher rate of suicide attempts among female. Males to females’ ratio are 1:1.19, a ratio that is in contrast to the distribution of completed suicides, where males are at higher risk than females.[12] Para suicides were most frequent in the young females’, i.e., 67.37% before 30 years old and 60% for males after 30 years old, Table 2, these findings are in line with previous cross-sectional data.[1314] In our society, which are regionally defined, mainly current antidepressants therapy then benzodiazepines is most probably due to its wide use and availability and organophosphorus which is also very cheep, available while salicylates and digitalis represented a small percentage of Para suicide attempts, Table 3.

The current work did not include Para suicides by means other than drugs intake, e.g., burn, drowning or falling from high; however, studies on Para suicide have reported that the commonest method by Para suicide is drug intake.[414] TCAs were detected in blood samples of patients using EMIT while the toxicological laboratory is lacking of measuring apparatus needed for detection of other types of antidepressants, e.g., SSRIs so, diagnosis of current treatment with types of antidepressants other than TCAs depended only on history taking and patient clinical condition. Overall, 63% of Para suicides were committed by patient taking TCAs, of which amitriptyline and dothiepin that are usually prescribed were responsible for the majority of cases. While about 27% was committed by patients taking SSRIs of which citalopram accounted for the majority of Para suicides, Table 4. Therefore, the present study revealed a decline in Para suicides among those taking SSRIs which are tolerable with fewer side effects. Most of the patients of our study was presented with Para suicide attempts within the first month of starting treatment with antidepressants, so the most explanation is that people tend to begin taking antidepressants when they are at their most depressed condition, and do not experience the benefits of the medications until several weeks have passed. Alternatively, it is possible that antidepressants cause depression to worsen before it is alleviated.

This study highlights the importance of closely monitoring people who are taking antidepressants especially during the fist month for worsening depression or emergence of suicidal thoughts or behaviors.[15] Adequate treatment with antidepressants is often useful in the treatment of moderately and severely depressed patients. Many recent studies, however, have revealed unidentification and under treatment of depression among suicide victims, and in suicide prevention, therapeutic failure rather than toxicity of antidepressants have been emphasized.[16] Therefore, much attention has been paid to the recognition of depressive disorders and the education of general practitioners, who have great responsibilities for identifying suicide risk, and who also prescribe the majority of antidepressants.[17]

The present results are in consistency with findings from several studies.[27-916] However,[10] in contrast to our results, found high risks and tendency to commit suicide with SSRIs. Whereas,[18] did not find any significant difference between SSRIs and TCAs in committing such Para suicide attempts.

CONCLUSIONS

The present study suggests that the use of certain antidepressants is indeed related to suicidal behavior with a substantial difference between different types of antidepressants. Para suicide risks for SSRIs were significantly lower than those of TCAs. TCAs accounted for a major part of Para suicides by antidepressants.

Recommendations

In Para suicide prevention, risks and benefits of antidepressants should therefore be taken into account with choosing treatment for depressive patients. Careful prescription of potentially lethal drugs is emphasized, and favoring drugs with a low risk is recommended whenever it is reasonable according to the patient's clinical condition.

The key principle of Para suicide prevention is increasing public awareness about the treatment of psychiatric disorders related to suicidal behavior.

The toxicological laboratory must be equipped with advanced apparatus essential for detection of recent drugs and other types of antidepressants, e.g., SSRIs.

Children with unintentional overdose should be admitted if inadequate supervision in the home is suspected or if adequate follow-up cannot be assured.

Further outpatient care

Patients may be discharged from the emergency department (ED) if the ingestion was accidental, if no signs or symptoms of CA toxicity are evident during a minimum observation of 6–8 h, if the parents are reliable, and if appropriate follow-up is assured.