Second edition

20.qxd 3/10/08 9:58 AM Page 641
abnormalities. Cerebrospinal fluid levels of CRH are
increased (Baker et al. 1999, 2005), and this is similar to
what is seen in major depressive disorder. However, the
cortisol response to dexamethasone, rather than being
blunted as is seen in depression, is enhanced in PTSD
(Goenjian et al. 1996; Yehuda et al. 1993, 2004).
Hippocampal atrophy has been demonstrated by some
(Bremner et al. 1995, 2003; Lindauer et al. 2006; Villarreal
et al. 2002), but not all (Bonne et al. 2001; Jatzko et al.
2006; Woodward et al. 2006), studies. The significance of
this finding is not clear. There are, at present, no prospective
MRI studies of patients before and after trauma, and
hence it is not clear if hippocampal atrophy precedes the
trauma and perhaps represents an underlying anatomic
vulnerability, or merely represents an epiphenomenon,
perhaps related to the physiologic effects of stress.
There is, apparently, only one neuropathologic study of
PTSD (Bracha et al. 2005). This study demonstrated a
reduction in neuronal cell number in the locus ceruleus in
PTSD patients compared with control subjects.
Overall, it appears reasonable to invoke a ‘stress–diathesis’
model for the etiology of PTSD. However, although the
‘stress’ is clear, the nature of the diathesis is not. It may be,
however, that there are changes in certain structures that
subserve emotional reactivity and remembrance, such as
the locus ceruleus and the hippocampus, which may in turn
be related to disturbances in catecholamine activity and the
function of the hypothalamic–pituitary–adrenal axis.
Differential diagnosis
After a significant trauma, rather than developing PTSD,
individuals may develop a major depressive disorder, and the
resulting depressive episode may at times be difficult to distinguish
from the symptoms seen in PTSD. Certain features,
however, may enable a differential diagnosis to be made.
Patients with depression have a depressed mood rather than a
sense of numbness or detachment; furthermore, patients
with depression may experience ruminations, which are
heavy, leaden recollections of misfortune, thus standing in
contrast to the starkly vivid and mercurial recollections and
flashbacks seen in PTSD. As noted earlier, patients with PTSD
may develop a depressive episode, but in these cases one sees
clear-cut PTSD preceding the onset of the depression.
In cases in which the original trauma was a head injury,
one must distinguish the features of a traumatic brain
injury or a post-concussion syndrome from PTSD, and
this may be difficult. Certainly, one cannot entertain the
diagnosis of PTSD in such cases unless patients display evidence
of involuntarily re-experiencing the original event,
such as vivid memories, nightmares or flashbacks. In posthead
trauma patients who do display such symptoms,
other symptoms, such as poor concentration, fatigue,
insomnia, lability, and irritability, may individually occur
secondary to a combined effect of the traumatic brain
injury (or post-concussion syndrome) and PTSD.
20.16 Generalized anxiety disorder 641
Malingerers and those with factitious illness, as discussed
in Section 7.8, may feign PTSD. In those feigning
combat-related PTSD, a review of military records may
reveal the lie; in cases, however, in which an actual trauma
did occur, for example a motor vehicle accident, the diagnosis
may have to wait upon resolution of pending litigation,
after which the ‘PTSD’ magically resolves.
Treatment
Cognitive–behavioral therapy appears to be effective.
Certain antidepressants are also effective, including
phenelzine (Frank et al. 1988), imipramine (Davidson et al.
1990), venlafaxine (Davidson et al. 2006), mirtazapine
(Davidson et al. 2003), and the SSRIs fluoxetine (Connor
et al. 1999; Martenyi et al. 2002; van der Kolk et al. 1994),
paroxetine (Marshall et al. 2001; Tucker et al. 2001), and
sertraline (Brady et al. 2000; Davidson et al. 2001),
(although not all studies are in agreement regarding the
effectiveness of fluoxetine [Martenyi et al. 2007] or sertraline
[Freidman et al. 2007]). Of the antidepressants, the
SSRIs have the longest track record, and one of these is generally
used first; consideration, however, may also be given
to mirtazapine or venlafaxine; imipramine is generally not
as well tolerated, and phenelzine is difficult to use.
Regardless of which antidepressant is chosen, a high dose
may be required, and at least 6 weeks should be allowed to
pass before assessing any effects. In cases in which the antidepressant
is either poorly tolerated or ineffective, consideration
may be given to switching to a different
antidepressant or, in patients on an SSRI, to augmentation
with either risperidone (1–2 mg) (Bartzokis et al. 2005;
Reich et al. 2004) or olanzapine (10 mg) (Stein et al. 2002);
of these two antipsychotics, risperidone is generally better
tolerated over the long haul and should probably be tried
first. Another medication to consider is prazosin. This
alpha-1 antagonist has been shown in double-blind work to
reduce the nightmares seen in PTSD (Raskind et al. 2003,
2007), and may be started at 1 mg in the evening, with the
dose increased in similar increments every few days until
patients obtain relief or limiting side-effects occur; most
patients respond to a dose of about 13 mg. There is also suggestive
work indicating that daytime prazosin may provide
further relief (Taylor et al. 2006). A non-blind study also
suggests that cyproheptadine, in a night-time dose of
4–12 mg, may reduce nightmares (Gupta et al. 1998).
As noted earlier, alcohol abuse or alcoholism not uncommonly
accompany PTSD, and when this is the case it is critical
to treat these, either first or concomitantly with the PTSD.
20.16 GENERALIZED ANXIETY DISORDER
Generalized anxiety disorder is characterized by a persistent,
‘free-floating’ anxiety, which is accompanied by autonomic
symptoms such as tremor. Although the lifetime prevalence