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Tricyclic antidepressants and serotonin reuptake inhibitors are
considered to be equally effective, but differences may have been
obscured by internally inconsistent measurement scales and inefficient
To test the hypothesis that escitalopram and nortriptyline differ in
their effects on observed mood, cognitive and neurovegetative symptoms of
In a multicentre part-randomised open-label design (the Genome Based
Therapeutic Drugs for Depression (GENDEP) study) 811 adults with moderate
to severe unipolar depression were allocated to flexible dosage
escitalopram or nortriptyline for 12 weeks. The weekly Montgomery–Åsberg
Depression Rating Scale, Hamilton Rating Scale for Depression, and Beck
Depression Inventory were scored both conventionally and in a more novel
way according to dimensions of observed mood, cognitive symptoms and
Mixed-effect linear regression showed no difference between escitalopram
and nortriptyline on the three original scales, but symptom dimensions
revealed drug-specific advantages. Observed mood and cognitive symptoms
improved more with escitalopram than with nortriptyline. Neurovegetative
symptoms improved more with nortriptyline than with escitalopram.
The three symptom dimensions provided sensitive descriptors of
differential antidepressant response and enabled identification of
Psychiatric disorders are common. The World Health Organization (WHO) estimates that at least one in four people will experience a clinically significant episode of psychiatric illness at some point in their lives. Although most such disorders are short lived and do not result in specialist care many cases become disabling and the WHO Global Burden of Disease Study (Murray and Lopez, 1997) has estimated that in health economic terms unipolar depression (UPD) vies with cardiovascular disease as the leading cause of disability in adults world wide. Schizophrenia and bipolar affective disorder (BPD) are also major public health problems which feature in the WHO's top ten of economically burdensome diseases. Between them, the affective disorders (UPD and BPD) and schizophrenia also account for over 60% of completed suicides. Therefore we will here focus on these three conditions as the main exemplars of common complex psychiatric disorders with substantial genetic contributions.
Clinical features and epidemiology
Unipolar depression (UPD) is so called because it consists of episodes of depressed mood whereas bipolar disorder (BPD) presents as episodes of both mania and depression. (A minority of patients with bipolar disorder have episodes of mania and no depressive episodes, but in terms of course, outcome, treatment response and pattern of illness in relatives they resemble typical bipolar disorder cases and are therefore classified as such rather than a “unipolar mania”).
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