Pharmacological heterogeneity within antidepressant classes
Rapid response to:
Fillers
Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis
Pharmacological heterogeneity within antidepressant classes
The paper by MacGillivray et al (BMJ 2003; 326: 1014) potentially
makes a huge contribution to the understanding of the relative utility of
serotonin selective reuptake inhibitors (SSRIs) and older antidepressants
in primary care. Sadly, the usefulness of this meta-analysis is limited by
the original data, as is so often the case. These results are very
difficult to interpret, not least because the comparitors used in the key
studies are pharmacologically heterogeneous. Two studies, including one of
the key three crucial studies providing data in an unambiguous format,
used mianserin as a comparitor. Mianserin is a tetracyclic, not a
tricyclic as the paper’s title might imply. It is not a potent reuptake
inhibitor and is a potent and thus sedative antihistamine. A third study
used lofepramine as a comparitor, more ‘modern’ tricyclic with a much more
benign anticholinergic side effect profile than its older cousins, with an
adverse event rate similar to the SSRIs (1).
Two of the three studies providing unambiguous data for the efficacy
analysis were of paroxetine against amitriptyline. Paroxetine may be
considered an ‘atypical’ SSRI, in that is has some adrenergic reuptake
inhibition and anticholinergic properties, so that pharmacologically is
has a profile lying between the more selective SSRIs and the classic
tricyclics, as does lofepramine (2).
As an underlying principle of meta-analysis is homogeneity of the
material, it is no surprise that a clear answer does not emerge from this
work, given the pharmacological heterogeneity.
References:
1. Katona CL, Abou-Saleh MT, Harrison DA, Nairac BA, Edwards DR, Lock
T, Burns RA, Robertson MM. Placebo-controlled trial of lithium
augmentation of fluoxetine and lofepramine. Br J Psychiatry. 1995
Jan;166(1):80-6.
2. Hale A S. The treatment of depression: the reuptake inhibitors.
In: Honig A, van Praag HM. Depression: Neurobiological, Psychopathological
and Therapeutic Advances. 1997. John Wiley & Sons Chichester UK.
Competing interests:
Past investigator and speaker for companies producing all the drugs concerned
Rapid Response:
Pharmacological heterogeneity within antidepressant classes
The paper by MacGillivray et al (BMJ 2003; 326: 1014) potentially
makes a huge contribution to the understanding of the relative utility of
serotonin selective reuptake inhibitors (SSRIs) and older antidepressants
in primary care. Sadly, the usefulness of this meta-analysis is limited by
the original data, as is so often the case. These results are very
difficult to interpret, not least because the comparitors used in the key
studies are pharmacologically heterogeneous. Two studies, including one of
the key three crucial studies providing data in an unambiguous format,
used mianserin as a comparitor. Mianserin is a tetracyclic, not a
tricyclic as the paper’s title might imply. It is not a potent reuptake
inhibitor and is a potent and thus sedative antihistamine. A third study
used lofepramine as a comparitor, more ‘modern’ tricyclic with a much more
benign anticholinergic side effect profile than its older cousins, with an
adverse event rate similar to the SSRIs (1).
Two of the three studies providing unambiguous data for the efficacy
analysis were of paroxetine against amitriptyline. Paroxetine may be
considered an ‘atypical’ SSRI, in that is has some adrenergic reuptake
inhibition and anticholinergic properties, so that pharmacologically is
has a profile lying between the more selective SSRIs and the classic
tricyclics, as does lofepramine (2).
As an underlying principle of meta-analysis is homogeneity of the
material, it is no surprise that a clear answer does not emerge from this
work, given the pharmacological heterogeneity.
References:
1. Katona CL, Abou-Saleh MT, Harrison DA, Nairac BA, Edwards DR, Lock
T, Burns RA, Robertson MM. Placebo-controlled trial of lithium
augmentation of fluoxetine and lofepramine. Br J Psychiatry. 1995
Jan;166(1):80-6.
2. Hale A S. The treatment of depression: the reuptake inhibitors.
In: Honig A, van Praag HM. Depression: Neurobiological, Psychopathological
and Therapeutic Advances. 1997. John Wiley & Sons Chichester UK.
Competing interests:
Past investigator and speaker for companies producing all the drugs concerned
Competing interests: No competing interests