Comorbidity anxiety/depression

Psychologist with psychiatry support, patient and family evaluation, formulation of comorbidities— anxiety, depression, delirium, counsels patients, family and team, knowledgeable in palliative care and end-of-life decision making... 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

Schneier, F. R., Blanco, C., Campeas, R., Lewis-Fernandez, R. el al. (2003). Citalopram treatment of social anxiety disorder with comorbid major depression. Depress. Anxiety, 17, 191-6. 

In a 6-week double-bhnd, placebo-controlled trial in patients diagnosed with comorbid anxiety and depression, Kramer et al. (1998) described the anxiolytic and antidepressant effects of the NKl antagonist, MK-869. 

Kessler RC (2001) Comorbidity of depression and anxiety disorders. In Montgomery SA, den Boer JA (eds) SSRIs in depression and anxiety. Wiley, Chichester, pp 87-106 Kessler RC, Price RH (1993) Primary prevention of secondary disorders a proposal and agenda. Am J Community Psychol 21 607-633 Kessler RC, McGonagle KA, Zhao S (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51 (1) 8-19... 

PTSD is highly comorbid with depression (Kessler et al. 1995) and substance use disorders, and is associated with a previous exposure to trauma and a previous history of anxiety disorders. PTSD probably carries the highest risk of suicide among the anxiety disorders (Davidson et al. 1991). Without effective treatment the disorder generally runs a chronic, unremitting course. 

Increased CRF-like immunoreactivity has also been measured in the CSF of patients with several anxiety disorders, including PTSD and obsessive-compulsive disorder, plausibly accounting for the frequent comorbidity among depression and anxiety disorders related... 

Kessler, R.C. and Walters, E.E. (1998) Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depress Anxiety 7 3-14. 

Comorbid anxiety has been associated with differential treatment response. This association predicts at times a better response to CBT and TCAs (Hughes et ah, 1990 Brent et ah, 1998). Treatment of comorbid anxiety, which most often precedes depression, is essential because the treatment contributes to improvement and may prevent future depressive episodes (Ko-vacs et ah, 1989 Hayward et ah, 2000). Fortunately, pharmacotherapy and psychotherapy treatments found useful for the treatment of MDD have also been found to be beneficial for treatment of youths with anxiety disorders (Kendall, 1994 RUPP Anxiety Group, 2001). 

Traditionally, SSRIs have been used in the treatment of depression. Yet we are discussing their use for treating anxiety. When two or more distinct mental disorders can be observed in the same person, the disorders are said to be comorbid. There is a high rate of comorbidity for depression and anxiety. Some 59.2% of people who have a major depressive disorder also have some form of an anxiety disorder. 

If there is a relationship between depression and anxiety, it is not surprising that certain drugs work to treat both. Ample evidence from both humans and animals suggests that the serotonergic system is altered in both types of disorders, and SSRI use is effective in the treatment of both disorders. It should be noted, however, that people who exhibit both disorders tend to be sicker for longer than those with only one disorder, and patients who have comorbid anxiety and depression do not respond as well to SSRI treatments. 

SRls are currently the most prevalent pharmacological treatment used for panic disorder [see Westenberg and Den Boer, Chapter 24, in this volume], even though tricyclic antidepressants, monoamine oxidase inhibitors [MAOls], and benzodiazepines are also effective. The efficacy of the SRI antidepressants and the observation that initially they may induce deterioration of symptoms [which is usually not the case with treatment of depressed patients with the same medications] raise issues related to the pathobiology of anxiety and its comorbidity with depression. 

This principle is not applicable in biological psychiatry. One can and should not simply discard the possibility that a biological variable observed in a psychotic condition is linked to a concurrent depression or that one found in depression is in fact related to a comorbid anxiety disorder. The hierarchical principle is a deus ex machina that resolves the problem of comorbidity only in appearance. Comorbidity in itself is merely a descriptive, not an explanatory, term. The multiplicity of psychiatric disorders, as they are presently defined, in so many patients permits a variety of explanations (Van Praag 1996], and thus the term comorbidity conceals more than it discloses. 

Comorbid anxiety and depressive features are common in clinical practice, and DSM-IV has included mixed anxiety-depression in its appendix of conditions needing nosological refinement. The presence of comorbid anxiety has prognostic implications. For example, prospective studies of patients with depression have found that the co-occurrence of panic attacks was correlated with a poor outcome (Coryell et al. 1988 van Valkenburg et al. 1984). Some evidence suggests that such patients do better with MAOls. Likewise, patients with depression and obsessive-compulsive disorder may be more resistant to treatment, even with SSRls (Hollander et al. 1991)... 

In human trials, reduced CSF concentrations have been observed among patients with depression. Upon their stratification into high or low levels of comorbid anxiety, the former demonstrated the most dramatic reductions in NPY [Widerlov et al. 1988]. Wahlestedt and colleagues [1993] have employed an innovative methodology to test the validity of this relationship by compromising brain NPY receptors via an antisense oligonucleotide. This knock-out resulted in an escalation of anxiety among test animals. 

Depressive and anxious symptoms are frequently associated with schizophrenia, but this does not necessarily mean that they fulfill the diagnostic criteria for a comorbid anxiety or affective disorder. Nevertheless, depressed mood, anxious mood, guilt, tension, irritability, and worry frequently accompany schizophrenia. These various symptoms are also prominent features of major depressive disorder, psychotic depression, bipolar disorder, schizoaffective disorder, organic dementias, and childhood... 

Several subtypes of depression require specific treatment strategies that go beyond a simple course of conventional antidepressant therapy (these subtypes include bipolar depression, major depression with psychotic features, seasonal depression, atypical depression, comorbid anxiety disorder, comorbid substance abuse, double depression [major depression... 

Anxiety disorders are quite prevalent in the general population and, of course, more so among patients in primary and specialty care. Also, some affect one gender more than the other (see Table 4.3). It is also common in clinical practice to see patients with symptoms that overlap two or more anxiety disorders or an anxiety disorder and another psychiatric condition for example, there is a high degree of comorbidity for depression and anxiety. 

Recently, Versiani et al. (1999) conducted a multicenter study involving 157 subjects in whom major depression and comorbid anxiety had been diagnosed. Subjects were randomly assigned to either fluoxetine therapy (20 mg/day) (n = 77) or amitriptyline therapy (50-250 mg/day) (n = 80). Patients were recruited from seven centers in five countries Brazil (n = 52), Mexico (n = 36),... 

The essential feature of panic disorder (PD)(13)is the occurrence of repeated, unexpected panic attacks. There is a marked worry about the consequences of the attack and the possibility of having a future attack. The persistent anxiety evoked by the panic attacks causes major behavioral changes and intrusion into normal life. Around 50% of panic disorder patients also suffer from agoraphobia. A lifetime prevalence of 3.5%has beenestimated (3), and a high comorbidity with depression and other anxiety disorders is observed. 

There is ample clinical evidence for the efficacy of the TCAs and MAOIs in almost all of the anxiety disorders, and these medications are perhaps most useful when such anxiety is comorbid with depression. In spite of this, patient acceptance and medical enthusiasm for these agents is muted by their slow onset of action and malignant side-effect profile (see below). Accordingly they are generally considered, at best, second-line medications. 

I Treatment of comorbid anxiety disorders has not been studied to the same extent as for depression. 

The anxiety disorders are a case in point. They comprise a range of conditions contiguous with the affective disorders and the stress responses (Table 4.1). Much overlap and comorbidity exist. Furthermore, definitions and diagnostic criteria have changed substantially over the years. For example, generalized anxiety disorder is a rare condition in its pure form, but a common condition if comorbid phobic and depressive disorders are accepted. 

Out-patient treatment is substantially cheaper than in-patient management and is generally as effective (Lowman, 1991). A French study on patients with generalized anxiety disorder estimated costs per patient over 3 months to he US 423 for hospitalization, 335 for out-patient services and 43 for medications (Souetre et al, 1994). Comorbid conditions (mostly alcoholism and depression) doubled these direct health-care costs. Over three-quarters of all patients were taking anxiolytic medication. 

---