© 2004 The Royal College of Psychiatrists
Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998–2000
Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, London
Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, London
Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, London
Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, London
Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, London
Correspondence: Survjit Cheeta, Department of Addictive Behaviour and Psychological Medicine, St George’s Hospital Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK. Tel: 020 8725 2635; fax: 020 8725 2914; e-mail: scheeta{at}sghms.ac.uk
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Background Deaths from antidepressants continue to account for a substantial proportion of drug-related deaths.
Aims To investigate the relative toxicity of the major classes of antidepressant drugs, with the specific objective of assessing this in relation to the cause of death; and to analyse the deaths where there were multiple mentions of antidepressant drugs or other psychoactive drugs with antidepressants.
Method Mortality data were collected from the National Programme of Substance Abuse Deaths, and antidepressant prescription data were collected.
Results Mostdeaths from antidepressant drugs were suicides (80%). Tricyclic antidepressants (TCAs) accounted for more drug mentions than did other antidepressant drugs (12 per million prescriptions). Selective serotonin reuptake inhibitors (SSRIs) were associated with a significantly lower risk of toxicity, but 93% of deaths from SSRIs occurred in combination with other drugs, especially TCAs (24.5%). In ‘combination’ deaths patients were significantly more likely to have had a history of drug misuse.
Conclusions The efficacy and safety of augmentation therapy with TCAsin SSRI-resistant patients should be monitored carefully, and patients prescribed antidepressants should be screened for drug use/misuse.
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Studies reporting on the toxicity of different antidepressants in overdose indicate that, compared with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, particularly amitriptyline and dothiepin, are associated with an increased risk from overdose (Henry et al, 1995; Shah et al, 2001). Although this information has aided in the choice of antidepressants prescribed, several questions remain about the profile of toxicity of different antidepressants. First, studies on antidepressant-related deaths have failed to distinguish between accidental deaths and deaths with suicidal intent. Furthermore, no studies have examined whether certain antidepressant drugs are more likely to be used in multiple drug overdoses, particularly in combination with other antidepressants or other psychoactive drugs. With this in mind, the aims of this paper were: to investigate the relative toxicity of the major classes of antidepressant drugs, with the specific objective of assessing the cause of death as either accidental or intentional; and to analyse deaths where other drugs were present in combination with antidepressants.
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Sources of data
The np-SAD database on drug-related deaths
In July 1997 the National Programme of Substance Abuse Deaths (np-SAD; Ghodse et al, 2002) was established after the Home Office’s index of addicts closed. Data are collected from coroners in England and Wales where licit or illicit psychoactive drugs are implicated in death. Coroners supply demographic data and information regarding the drugs implicated in these fatalities.
Prescription cost analysis
Prescription cost analysis provides details on the total quantity, number
of prescription items and net ingredient cost of all antidepressant
prescriptions dispensed in the community by doctors in England (Department of
Health, Statistics Division 1E, Prescription Cost Analysis system) and Wales
(Prescribing Services Unit, Health Solutions, Wales) during 1998–2000.
Prescriptions written by hospital doctors are also included provided that they
were dispensed in the community. Prescription cost analysis uses the concept
of the ‘defined daily dose’, which is an international system
developed by the World Health Organization, and is defined as ‘the
assumed average maintenance dose per day for a drug used on its main
indication in adults’. It also collects information on ‘average
daily quantity’ for antidepressants, a concept developed by an expert
group convened by the Prescribing Support Unit and used to reflect more
adequately general practitioner prescribing in England, based on several
measures, including defined daily doses and British National
Formulary information. Prescription cost analysis does not cover items
dispensed in hospitals or on private prescriptions. However, because
90–98% of patients with depression are seen by general practitioners
rather than psychiatrists (Thompson &
Thompson, 1989; McCarthy,
1993; Donoghue & Tylee,
1996; Dunn et al,
1999; Middleton et
al, 2001), the exclusion of private prescriptions and
hospital-dispensed prescriptions from our analysis should not appreciably
affect the outcome of this study.
Study population
The study population consisted of cases reported by coroners in England and
Wales to the np-SAD for deaths occurring during the 3-year period
1998–2000. Cases for the study were those who had a current prescription
for antidepressant drugs at the time of the fatality and where antidepressant
drugs were implicated in the cause of death. Contribution to fatalities is
defined by the np-SAD as being when substances are specifically mentioned in
the cause of death by the coroner, or when the drug type in the cause of death
is not specified (e.g. ‘polydrug toxicity’) but the coroner
reports that drugs were present post-mortem. Cases are classified as
intentional in the np-SAD database according to the coroner’s verdict of
‘suicide’ or ‘open’ where suicide is likely. For the
purposes of this study, ‘accidental’ includes deaths by accidental
overdose, traumatic accident or acute medical conditions. Cases are also
classified as those with or without a drug misuse history.
Data analysis
Antidepressants were assigned to four therapeutic classes according to the
British National Formulary: tricyclic antidepressants, monoamine
oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs)
and other antidepressant drugs. The antidepressants included in each
therapeutic class can be seen in Table
2. For each of the above classes of antidepressant, the following
variables were analysed:
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View this table: [in a new window] | Table 2 Number of drug mentions by specific drug and per million prescriptions in England and Wales, 1998-2000 |
- frequencies of drug mentions per million prescriptions; the observed number
of mentions was compared with the expected number of mentions, which was
calculated by standardising for the number of prescriptions;
- frequencies of mentions in deaths by single drug or in combination with
other drugs;
- other drugs most likely to be implicated in deaths in combination with
antidepressants;
- history of drug misuse or dependence;
- the incidence of antidepressants by class in accidental and intentional
deaths.
Statistical analysis
We used prevalence ratios and their 95% confidence intervals (CIs) to
compare differences in proportions. Standardised mortality ratios and their
95% CIs were used to compare observed and expected number of deaths when
standardised for the number of prescriptions for antidepressant drugs. The
2 statistical test was used to test for differences between
the antidepressant therapies. All analyses were undertaken using the
Statistical Package for the Social Sciences for Windows version 1.0 and
CLINISTAT (Bland, 1990).
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Antidepressant classes implicated in death compared with the number of prescriptions
During the study period there were 4167 drug-related deaths, of which 468 had an antidepressant implicated in the deaths. Therefore, 11.2% of all drug-related deaths involved antidepressant drugs. Among the 468 fatalities there were 473 mentions of antidepressants by class implicated in the deaths. A total of 285 cases had a single antidepressant class implicated in the deaths and there were 186 cases where two or more specific drug types were implicated: an antidepressant class and another drug or multiple mentions of antidepressants with or without other drugs. There were 498 mentions of specific antidepressants and there were 10 cases that had a mention of both nortriptyline and amitriptyline. Because nortriptyline is a metabolite of amitriptyline (Sanchez & Hyttel, 1999) these cases were included in fatalities associated with amitriptyline only.
There was a substantial variation in the risk of death from the different antidepressant classes when compared with the number of prescriptions. As can be seen from Table 1, the tricyclics (12 mentions per million prescriptions) and the MAOIs (14 mentions per million prescriptions) had a higher number of mentions per million prescriptions compared with the SSRIs (2 mentions per million prescriptions). The tricyclics prescribed most frequently were dothiepin, amitriptyline and lofepramine. Both dothiepin and amitriptyline were associated with significantly more deaths than would be expected when standardised for the number of prescriptions but lofepramine was associated with significantly fewer mentions. In contrast to amitriptyline and dothiepin, the SSRIs were associated with significantly fewer mentions than would be expected (P<0.0001) when standardised for the number of prescriptions, and this was the case for the four most widely prescribed SSRIs: fluoxetine, paroxetine, citalopram and sertraline (Table 2). For the class of other antidepressant drugs, 88% of fatalities were due to venlafaxine and the remainder were due to trazodone, which was associated with significantly fewer mentions than would be expected (P<0.05) when standardised for the number of prescriptions. Venlafaxine, however, had a mortality rate not dissimilar to that seen with the tricyclics, and there were 13 mentions per million prescriptions of this drug (see Table 2).
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View this table: [in a new window] | Table 1 Number of mentions of antidepressants by class per million prescriptions in England and Wales, 1998-2000 |
Antidepressants in combination with other drugs implicated in mortality
Of 468 deaths in which antidepressant drugs were implicated, 60% had
antidepressants solely implicated in death, whereas antidepressants in
combination with other drugs were implicated in 40% of cases. There was a
significant relationship between whether antidepressants were implicated alone
or in combination with other drugs and the type of antidepressant
(2=55.39, P<0.0001), and antidepressant-related
fatalities involving multiple drug mentions were almost three times more
likely to occur in SSRI-related cases than in tricyclic-related cases
(percentage ratio=2.7, 95% CI 2.3–3.2; see
Table 3). As can be seen from
Table 4, the most frequently
mentioned drugs in combination with SSRIs were alcohol (26%), tricyclic
antidepressants (24%) and other opiates (24%). Antipsychotics (12%) were also
implicated. When tricyclics were found in combination with other drugs in
antidepressant-related deaths, the other drugs most likely to be implicated
were alcohol (41.4%), other opiates (20.7%), SSRIs (8.6%), heroin (8.6%) and
methadone (7.1%). A different profile emerged for the class of other
antidepressants, where antipsychotics (38.9%), alcohol (27.8%) and other
opiates (16.7%) were most likely to be found in combination.
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View this table: [in a new window] | Table 3 Classes of antidepressant drugs implicated in deaths between 1998 and 2000 either alone or in combination with other drugs |
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View this table: [in a new window] | Table 4 Frequencies of antidepressants by class associated with other common psychoactive drugs and other antidepressants1 |
Drug misuse status of antidepressant-implicated deaths
Deaths related to antidepressant use in combination with other drugs were
more likely to occur among drug misuse cases than non-drug misuse cases
(2=20.87, P<0.0001). However, among these
‘combination’ deaths there was no evidence that being a drug
misuser was related to a particular class of antidepressant
(2=1.55, P=0.4).
Accidental and intentional antidepressant deaths
As can be seen from Table 5,
20% of mentions were associated with accidental deaths whereas 80% of mentions
were associated with intentional deaths, suggesting that most deaths from
antidepressant drugs are due to suicide. Tricyclic antidepressants are
associated with a higher number of accidental and intentional deaths, and
significantly more accidental (P<0.0001) and intentional
(P<0.001) deaths were observed with the tricyclics than would be
expected when standardised for the number of prescriptions. The SSRIs were
associated with significantly fewer accidental (P<0.0001) and
intentional (P<0.0001) deaths than would be expected when
standardised for the number of prescriptions. For the other antidepressant
drugs there was no significant difference between the number of observed and
expected mentions when standardised for the number of prescriptions. Finally,
there was no evidence of a relationship between type of antidepressant and the
occurrence of an intentional or accidental death.
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View this table: [in a new window] | Table 5 Frequencies of drug mentions by class in accidental and intentional deaths |
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Fatalities related to tricyclic antidepressants
The present study suggests that up to 80% of deaths from antidepressants are suicides, and confirms previous findings that the tricyclics most likely to be implicated in antidepressant-related deaths are amitriptyline and dothiepin. Although the antidepressant properties of tricyclics are attributed to their ability to inhibit both noradrenalin and serotonin reuptake, it has been suggested that the increased toxicity of these drugs in overdose may be due to modulation of ion channel function within the myocardium. Indeed the tricyclics, particularly amitriptyline, have been associated with the inhibition of both cardiac sodium (Na+) channels and potassium (K+) channels, which is associated with an increased risk of cardiac arrthymias and sudden death (Freeman et al, 1969; Marshall & Forker, 1982; Ma & Henry, 2001; Witchel et al, 2003). Lofepramine was the only tricyclic associated with a lower incidence of mortality. Although the mechanism of the lower toxicity of this drug has yet to be clarified, its membrane-stabilising activities (which may increase the risk of cardiac arrthythmias) are much lower than those of amitriptyline and desipramine (Darcy et al, 2002).
Fatalities related to selective serotonin reuptake inhibitors
In contrast to amitriptyline and dothiepin, this study clearly suggests
that the SSRIs when taken on their own are safer in overdose and are less
likely to be implicated in both intentional and accidental deaths. In addition
to the treatment of depression, antidepressant drugs have been used for many
other indications. In particular, SSRIs have been used in the treatment of
generalised anxiety disorders, obsessive–compulsive disorders, social
phobia, premenstrual dysphoric disorder and post-traumatic stress disorder
(Ables & Baughman, 2003).
Because these disorders are likely to carry a lower risk of suicide than
depressive illnesses, this could also account for the reduced toxicity of
these drugs in overdose. The present study suggests that when SSRIs are
implicated in death they are mostly found in combination with other drugs,
especially with tricyclics. In clinical practice, augmentation therapy
involving the prescription of an antidepressant alongside another
antidepressant drug of the same or different pharmacological class has largely
been used in patients with treatment-resistant depression or in patients who
only partially respond to antidepressants
(Fava, 2001). Therefore, a
possible explanation for the increased number of combination deaths with SSRIs
is that these individuals were suffering from a treatment-resistant depression
and tricyclics may have been prescribed concurrently, accounting for the fatal
outcome. The SSRIs have been shown also to differ in the extent of their
inhibition of the cytochrome P-450 enzymes of the liver, which are crucial in
the metabolism of numerous drugs
(Richelson, 1997), raising the
possibility of drug–drug interactions in patients taking multiple
medications. Enzyme CYP2D6 is considered the principal P-450 cytochrome enzyme
in the clearance of tricyclics, and data from in vitro studies
suggest that the rank order of potency for inhibition of CYP2D6 by
antidepressants is paroxetine 
fluoxetine > sertraline > fluvoxamine
> venlafaxine > mirtazapine
(Vaughan, 1988;
Crewe et al, 1992).
Therefore, it is possible that by inhibiting CYP2D6 the SSRIs may increase
plasma levels of tricyclics, thereby increasing the toxic effects associated
with these drugs. This could be an explanation for the present findings of
increased risk of death from SSRIs in combination with tricyclics, although
the data at present do not seem to support this hypothesis because higher
rates of deaths involving SSRIs such as fluoxetine and paroxetine were not
found. Although we do not know what percentage of the combination deaths from
SSRIs and tricyclics occurred as a result of prescription within the normal
clinical guidelines, the present findings do suggest that the clinical
efficacy of augmentation therapy in SSRI-resistant patients should be
monitored carefully because of the risk of suicide.
Antidepressant-related deaths and drug misuse
The present study is the first to demonstrate that cases involving
antidepressants with other drugs are significantly more likely to involve drug
addicts. The other drugs that are most likely to be implicated in combination
with the antidepressants were alcohol and opiate-based drugs. These findings
suggest that general practitioners and psychiatrists should screen for drug
use/misuse patterns in patients being prescribed antidepressants and should
prescribe cautiously for these individuals.
Venlafaxine-related fatalities
This study suggests that, of the miscellaneous group of antidepressants,
venlafaxine may be more toxic in overdose than other drugs in this class. This
finding supports evidence from a recent study published by Buckley &
McManus (2002). Venlafaxine is
a serotonin and noradrenalin reuptake inhibitor and at low doses is very
similar to SSRIs in that it predominantly inhibits the reuptake of serotonin,
although at higher doses noradrenalin reuptake inhibition is predominant.
Furthermore, recent case studies have suggested a link between cardiac
illness/failure and venlafaxine, and there is evidence that this drug blocks
Na+ channels (Blythe &
Hackett, 1999; Khalifa et
al, 1999; Reznik et
al, 1999; Drent et
al, 2003). However, the other drugs most likely to be found
in combination with venlafaxine were antipsychotics, which were implicated in
38.9% of cases in this group. The higher rate of antipsychotic prescribing
with venlafaxine suggests that a different patient group may have been
involved, possibly the seriously depressed or dual-diagnosis patients who are
difficult to treat and possibly at a greater risk from suicide.
Limitations and summary
It is important to note that there are several reasons apart from the
toxicity of antidepressant medication that can lead to a fatal overdose. These
include treatment-resistant depression, non-response to the antidepressant
therapy, medication non-compliance, duration of illness, history of
antidepressant treatments and undertreatment of depression. Previously it has
been suggested that in primary care practice tricyclic antidepressants are
frequently prescribed at doses below those that are shown to be efficacious in
randomised controlled clinical trials
(Donoghue & Taylor, 2000), with studies showing that up to 88% of patients receiving tricyclics were on
doses below those recommended in the national guidelines
(Donoghue & Tylee, 1996).
However, a recent meta-analysis of randomised controlled clinical trials
comparing the effects of low-dose and standard-dose tricyclics suggests that
low dosage regimes are more effective than placebo in the treatment of
depression, and may or may not be as effective as standard dosage regimes but
that the drop-out rate is lower because they produce fewer side-effects
(Furukawa et al,
2002). This is in contrast to the SSRIs, which are associated with
the lowest level of mortality and are almost always prescribed at efficacious
doses in primary care settings (Donoghue
& Tylee, 1996; Dunn et
al, 1999). Furthermore, not all coroners report to the np-SAD
database, although the response rate from the coroners in England and Wales
has been estimated to be as high as about 95%
(Oyefeso et al,
1999). Despite these limitations, the present study clearly
suggests that, although tricyclic antidepressants are more toxic in overdose,
the SSRIs are largely implicated in death in combination with other drugs,
especially tricyclics, suggesting either a treatment-resistant depression or
non-response to pharmacotherapy. Therefore, suicide risk should be monitored
carefully when augmentation therapy is used in SSRI-resistant patients.
Furthermore, all patients prescribed antidepressants should be screened
routinely for a history of drug use/misuse.
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CLINICAL IMPLICATIONS
- Because 80% of deaths from antidepressants are intentional, suicide risk
needs to be monitored carefully in all patients prescribed antidepressant
drugs.
- Although selective serotonin reuptake inhibitors (SSRIs) are safer in
overdose than the tricyclic antidepressants, deaths in which SSRIs are
implicated are most likely to be in combination with other drugs, particularly
tricyclics. Therefore, the efficacy and safety of augmentation therapy in
SSRI-resistant patients should be monitored carefully.
- Deaths in which antidepressants are implicated in combination with other
drugs are more likely to happen in drug misusers. Therefore, all patients
prescribed antidepressants should be screened routinely for a history of drug
use/misuse.
LIMITATIONS
- Because not all coroners report to the National Programme of Substance
Abuse Deaths database, the number of deaths in which antidepressant drugs are
implicated is likely to be underestimated.
- Factors other than the antidepressant medication, such as medication
non-compliance, undertreatment of depression and non-response to
antidepressant therapy, may have led to the fatal outcome.
- Toxicology reports on the quantity of drug detected at post-mortem
examination were not available.
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- Ables, A. Z. & Baughman, O. L. (2003) Antidepressants: update on new agents and indications. American Family Physician, 67, 547 –554.[Medline]
- Bland, J. M. (1990) CLINSTAT Users’ Guide. London: St George’s Hospital Medical School.
- Blythe, D. & Hackett, L. P. (1999)
Cardiovascular and neurological toxicity of venlafaxine. Human and
Experimental Toxicology, 18, 309
–313.
[Abstract/Free Full Text] - Buckley, N. A. & McManus, P. R. (2002)
Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of
United Kingdom mortality data. BMJ,
325, 1332
–1333.
[Free Full Text] - Crewe, H. K., Lennard, M. S., Tucker, G. T., et al (1992) The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. British Journal of Clinical Pharmacology, 34, 262 –265.[Medline]
- Darcy, P., Kelly, J. P., Leonard, B. E., et al (2002) The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis. Toxicology Letters, 128, 207 –214.[CrossRef][Medline]
- Donoghue, J. M. & Tylee, A. (1996) The
treatment of depression: prescribing patterns of antidepressants in primary
care in the UK. British Journal of Psychiatry,
168, 164
–168.
[Abstract/Free Full Text] - Donoghue, J. M. & Taylor, D. M. (2000) Suboptimal use of antidepressants in the treatment of depression. CNS Drugs, 13, 365 –383.[CrossRef]
- Drent, M., Singh, S., Gorgels, A. P., et al
(2003) Drug-induced pneumonitis and heart failure
simultaneously associated with venlafaxine. American Journal of
Respiratory and Critical Care Medicine,
167, 958
–961.
[Abstract/Free Full Text] - Dunn, R. L., Donoghue, J. M., Ozminkowski, R. J., et al
(1999) Longitudinal patterns of antidepressant prescribing in
primary care in the UK: comparison with treatment guidelines.
Journal of Psychopharmacology,
13, 136
–143.
[Abstract/Free Full Text] - Fava, M. (2001) Augmentation and combination strategies in treatment-resistant depression. Journal of Clinical Psychiatry, 62 (suppl. 18), 4 –11.
- Freeman, J.W., Mundy, G.R., Beattie, R.R., et al
(1969) Cardiac abnormalities in poisoning with tricyclic
antidepressants. BMJ, 2, 610
–611.
[Abstract/Free Full Text] - Furukawa, T. A., McGuire, H. & Barbui, C.
(2002) Meta-analysis of effects and side effects of low
dosage tricyclic antidepressants in depression: systematic review.
BMJ, 325, 991
–999.
[Abstract/Free Full Text] - Ghodse, H., Oyefeso, A., Webb, L., et al (2002) Drug-related Deaths as Reported by Coroners in England and Wales, January–June 2001 (np-SAD Surveillance Report no. 8). London: St George’s Hospital Medical School.
- Henry, J. A., Alexander, C. A. & Sener, E. K.
(1995) Relative mortality from overdose of antidepressants.
BMJ, 310, 221
–224.
[Abstract/Free Full Text] - Khalifa, M., Daleau, P. & Turgeon, J.
(1999) Mechanism of sodium channel block by venlafaxine in
guinea pig ventricular myocytes. Journal of Pharmacology and
Experimental Therapeutics, 291, 280
–284.
[Abstract/Free Full Text] - Ma, Y. & Henry, J. A. (2001) The antidotal effect of alpha(1)-acid glycoprotein on amitriptyline toxicity in cardiac myocytes. Toxicology, 169, 133 –144.[CrossRef][Medline]
- Marshall, J. B. & Forker, A. D. (1982) Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. American Heart Journal, 103, 401 –414.[CrossRef][Medline]
- McCarthy, M. (1993) Depression treatment guidelines (letter). Lancet, 341, 1087.
- Middleton, N., Gunnell, D., Whitley, E., et al
(2001) Secular trends in antidepressant prescribing in the
UK, 1975–1998. Journal of Public Health
Medicine, 23, 262
–267.
[Abstract/Free Full Text] - Oyefeso, A., Ghodse, H., Clancy, C., et al
(1999) Suicide among drug addicts in the UK.
British Journal of Psychiatry,
175, 277
–282.
[Abstract/Free Full Text] - Reznik, I., Rosen, Y. & Rosen, B. (1999) An
acute ischaemic event associated with the use of venlafaxine: a case report
and proposed pathophysiological mechanisms. Journal of
Psychopharmacology, 13, 193
–195.
[Abstract/Free Full Text] - Richelson, E. (1997) Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs. Mayo Clinic Proceedings, 72, 835 –847.[Abstract]
- Sanchez, C. & Hyttel, J. (1999) Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cellular and Molecular Neurobiology, 19, 467 –489.[CrossRef][Medline]
- Shah, R., Uren, Z., Baker, A., et al (2001) Deaths from antidepressants in England and Wales 1993–1997: analysis of a new national database. Psychological Medicine, 31, 1203 –1210.[CrossRef][Medline]
- Thompson, C. & Thompson, C. M. (1989) The prescribing of antidepressants in general practice: II. A placebo controlled trial of low dose dothiepin. Human Psychopharmacology, 4, 191 –204.[CrossRef]
- Vaughan, D. A. (1988) Interaction of fluoxetine with tricyclic antidepressants. American Journal of Psychiatry, 145, 1478 .
- Witchel, H. J., Hancox, J. C. & Nutt, D. J. (2003) Psychotropic drugs, cardiac arrhythmia, and sudden death. Journal Clinical of Psychopharmacology, 23, 58 –77.[CrossRef][Medline]
Related articles in BJP:
- Highlights of this issue
- SUKHWINDER S. SHERGILL
BJP 2004 184: 1-a3.[Full Text]
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 S. Wessely and R. Kerwin Suicide Risk and the SSRIs JAMA, July 21, 2004; 292(3): 379 - 381. [Full Text] [PDF]
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