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Australian Journal of Pharmacy : June 2005
CDI_LH_Jun05.qxd 13/05/2005 12:43 PM Page 5 pharmacy ed u cdi: drug review • approved CPE Diagnosis of depression For a patient to be diagnosed with major depression, five or more of the following symptoms have to be present for greater than two weeks.4 • depressed mood; • decreased interest or pleasure in all or most activities; • significant weight loss or gain not due to dieting; • insomnia or hypersomnia; • psychomotor agitation or retardation; • fatigue or loss of energy; • feelings of worthlessness or inappropriate or excessive guilt; • diminished ability to think or concentrate or indecisiveness; and • recurrent thoughts of death, suicidal ideation, plan or attempt. For depression to be diagnosed, at least one of the above symptoms has to be depressed mood or loss of pleasure; the symptoms must cause clinically significant distress or impairment in social, occupational or other important areas of functioning; and the symptoms must not be due to the direct physiological effect of exogenous substances. It must also be excluded that the symptoms are not better accounted for by bereavement, and a patient with depression that is precipitated by death of a loved one is only diagnosed with depression after about six months, if the patient is still exhibiting depressive symptoms after this time. Symptoms and signs of depression The symptoms and signs of depression can be classified under psychological, functional and behavioural streams and are included in the listings below:4 Psychological Functional • low mood, sadness • guilt, worthlessness • hopelessness • loss of pleasure • loss of interest • sleep disturbance • change in appetite • loss of libido • diurnal variation • weight change • increased anxiety, worry • psychomotor retardation • thoughts of death • suicidal thoughts • loss of confidence Behavioural • social withdrawal • reduced activity • frequent crying • restlessness, pacing • indecisiveness • increased alcohol use • self-harm, suicide attempts • inability to perform everyday duties Antidepressant drug classes In the past 10 years many new drug classes of antidepressants have been introduced onto the market. The classes of antidepressants on the market include: • Tricyclic antidepressants (TCAs). 480 THE AUSTRALIAN JOURNAL OF PHARMACY, VOL.86 JUNE 2005 Low sedation - Moderate sedation Imipramine Clomipramine nortriptyline High sedation Amitriptyline Dothiepin Doxepin Trimipramine Adverse effects of anticholinergic activity include both central and peripheral anticholinergic effects. Central anticholinergic • reduced concentration, memory • constipation • Alpha-2 blockers (mianserin). • Monoamine oxidase inhibitors (MAOIs). • Reversible inhibitors of monoamine oxidase A (RIMAs) (moclobemide). • Selective serotonin reuptake inhibitors (SSRIs). • Serotonin and noradrenaline reuptake inhibitors (SNRIs) (venlafaxine). • Serotonin 5HT2 receptor blockers (nefazodone, mirtazapine). • Selective noradrenaline reuptake inhibitors (reboxetine). Generic name Amitriptyline Clomipramine Dothiepin Doxepin Imipramine Nortriptyline Trimipramine Brand name Endep Tryptanol Tryptine Anafranil Placil Prothiaden Dothep Sinequan Tofranil Melipramine Allegron Surmontil Mechanism of action The TCAs inhibit reuptake of noradrenaline, and to a lesser extent serotonin, into the synapse.8 This is the same mechanism by which other amines are disposed of, notably the OTC decongestants phenylephrine and pseudoephedrine.9 Thus combining TCAs with these OTC drugs can increase their effects by inhibiting their breakdown, causing dangerous increases in blood pressure. The increase in noradrenaline at synaptic junction occurs immediately, but the onset of antidepressant effect occurs in two to four weeks, which is more in line with alteration of receptor proteins and receptor downgrading.8 However, the TCAs have affinity for many other receptor types, including histamine blockade, acetylcholine receptor blockade, alpha-receptor blockade and a direct effect on heart musculature.4 Blockade of these receptors is associated with a range of adverse effects. This has led to the TCAs, while effective for depression, not being first choice of drug for depressive disorders. Tricyclic antidepressant sedative effects are due to histamine blockade.