Depression and anxiety

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

Promoting an Optimal Response to Therapy Superficial and deep fungal infections respond slowly to antifungal therapy. Many patients experience anxiety and depression over the fact that therapy must continue for a prolonged time Depending on the method of treatment, patients may be faced with many problems during therapy and therefore need time to talk about problems as they arise Examples of problems are the cost of treatment, hospitalization (when required), the failure of treatment to adequately control the infection, and loss of income. The nurse must help the patient and the family to understand that therapy must be continued until tlie infection is under control. In some cases, therapy may take weeks or months. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

F43.2 Adjustment disorders. 20 Brief depressive reaction. 21 Prolonged depressive reaction. 22 Mixed anxiety and depressive reaction. 23 With predominant disturbance of other emotions. 24 With predominant disturbance of conduct. 25 With mixed disturbance of emotions and conduct. 28 With other specified predominant symptoms... 

The usually accepted prevalences for generalized anxiety disorder (GAD) are around 1.6% for current, 3.1% for 1 year and 5.1% lifetime (Roy-Byrne, 1996). The condition is twice as common in women as in men (Pigott, 1999). A small minority (10%) have GAD alone, and about the same proportion suffer from mixed anxiety and depression. Morbidity is high. About a half of those with uncomplicated GAD seek professional help, but two-thirds of those with comorbid GAD do so. Up to a half take medication at some point. The condition may coexist with other anxiety disorders such as phobias, with affective disorders, or with medical conditions such as unexplained chest pain and irritable bowel syndrome. 

Graeff, FG, Guimaraes, FS, De Andrade, TGC and Deakin, JFW (1996) Role of 5-HT in stress, anxiety and depression. Pharmacol. Biochem. Behav. 54 129-141. 

Elliott, JM (1992) Peripheral markers in anxiety and depression. Molec. Aspects Med. 13 173-190. 

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. 

As we have seen, low doses of caffeine (75 to 300 mg) have been shown to increase positive mood states,153 with higher doses leading to more and more positive mood states, at least up to a point.155-265 At the very high levels of consumption (greater than 500 mg) seen in heavy caffeine users,157 the drug can elevate anxiety and depress affect.34 Our more general review of the mood state literature above leaves little doubt that caffeine is a psychoactive drug. 

When we began using reserpine at the Maudsley Hospital less than two years ago there were very few reliable accounts of its use in the treatment of neuropsychiatric conditions and almost no controlled clinical studies. Dr D. L. Davies and I therefore conducted a clinical trial on a mixed group of out-patients, the majority of whom were suffering from anxiety and depressive reactions. The patients were given either reserpine, prescribed as Serpasil in a dose of 0.5 mg. by mouth twice daily, or a seemingly identical placebo, for a period of six weeks. The two substances... 

One of the factors that determine the effectiveness of a placebo is the nature of the condition being treated. Conditions that have a strong psychological component - such as pain, anxiety and depression - are particularly prone to placebo influence, whereas conditions like bone fractures, diabetes and infertility are less likely to be affected by placebo treatment. But this does not mean that placebo effects are all in the mind . Placebos affect physiology as well as psychology. 

This type of action is found in kanna, or Sceletium expansum and Sceletium tortuosum (Aizoaceae), which have been used by South African shamans from prehistoric times to enhance animal spirits, sparkle the eyes, and to stimulate gaiety. The active constituent of kanna is a serotonin-like alkaloid called mesembrine, which is a potent serotonin re-uptake inhibitor—hence, some potential for the treatment of anxiety and depression however, careful clinical trials must be performed. 

The problems of alcohol dependence and alcoholism are dealt with in Chapter 10. Suffice it to say here that problem drinkers risk numerous psychological problems, such as anxiety and depression, and may experience physical withdrawal symptoms. There are also numerous medical problems related to heavy, chronic alcohol consumption these include increased risk of coronary heart disease, liver cirrhosis, impotence and infertility, cancer and stroke (Chapter 10). It is estimated that alcohol plays a part in up to 33,000 deaths per year in the UK (DoH, 2001). Within the last year 1 in 4 adults will have experienced loss of memory following an alcoholic binge, injured themselves or... 

Panic disorder Agoraphobia with panic disorder Agoraphobia without panic disorder Specific phobia Social phobia Generalised anxiety disorder Mild anxiety and depression disorder Obsessive compulsive disorder Acute stress disorder Post-traumatic stress disorder (PTSD) Adjustment disorder Panic disorder without agoraphobia Panic disorder with agoraphobia Agoraphobia Specific phobia Social phobia (also called social anxiety disorder) Generalised anxiety disorder Obsessive compulsive disorder Acute stress disorder Post-traumatic stress disorder (PTSD)... 

Sandler M (1992). Development of anxiolytic and antidepressant drugs A historical perspective. In JM Elliot, DJ Heal and CA Marsden (eds), Experimental Approaches to Anxiety and Depression (pp. 1-8). John Wiley Sons, Chichester, UK. 

Patients with anxiety and depression often have bowel symptoms. Gorad et al. compared 21 psychiatric outpatients with generalized anxiety disorders and depression with an equal number of healthy controls. Whole-gut transit time (WGTT) was measured using abdominal radiography after ingestion of radioopaque markers, and found to be shorter in patients with anxiety (mean 14 h ... 

Clark, L. A., Watson, D. (1991). Tripartite model of anxiety and depression Psychometric evidence and taxonomic implications. Journal of Abnormal PsychoP ogy, 100, 316-336. 

Beck Depression Inventory. The Beck Depression Inventory (Beck) test may be used to measure the depth of depression as a rapid screen for depressed patients. It is a self-rating scale of 21 items (13 in a shortened form), with each item rated on a four-point scale. It measures the immediate present and has been used in antidepressant medicine trials. The original 21-item scale can be completed in about 10 minutes and the test is able to discriminate between anxiety and depression. No subtests are present in the Beck. 

Long-term health effects from exposure to low-to-moderate doses of radiation include cancer of the thyroid, prostate, kidney, liver, salivary glands, and lungs Hodgkin s disease leukemia and increased numbers of stillbirths and genetic defects. Concerns about potential long-term health effects often lead to anxiety and depression problems among those exposed to radiation. 

Becker, O.M., Dhanoa, D.S., Marantz, Y., Chen, D., Shacham, S., Cheruku, S., Heifetz, A., Mohanty, P., Fichman, M., Sharadendu, A., Nudelman, R., Kauffman, M. and Noiman, S. (2006) An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. Journal of Medicinal Chemistry, 49, 3116-3135. 

A specific example of the problems that arise from insuffident selectivity and affinity to off-target proteins is that many of the currently approved drugs for the treatment of anxiety and depression have troublesome side effects. According to the... 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Izard, C. E. (1972). Patterns of Emotions A new analysis of anxiety and depression. New York Academic Press. 

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