{"id":148,"date":"2019-10-07T20:04:07","date_gmt":"2019-10-07T14:34:07","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=148"},"modified":"2019-10-07T20:04:07","modified_gmt":"2019-10-07T14:34:07","slug":"antidepressant-drugs","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/antidepressant-drugs\/","title":{"rendered":"Antidepressant Drugs"},"content":{"rendered":"\n

Antidepressant Drugs<\/strong><\/p>\n\n\n\n

Depression\nresults due to decreased monoaminergic (5-HT and NA<\/em>) activity in the\nbrain, therefore drugs increasing <\/em>their activity are called typical\nanti-depressants<\/strong>. <\/p>\n\n\n\n

Drugs acting by other mechanisms are called atypical anti-depressants<\/strong>.<\/p>\n\n\n\n

\"\"<\/figure><\/div>\n\n\n\n

A. Typical Antidepressants<\/h1>\n\n\n\n

Drugs may\nincrease monoaminergic transmission by inhibiting the reuptake or metabolism\n<\/em>of 5-HT or NA.<\/p>\n\n\n\n

1. Tricyclic Antidepressants (TCA)<\/h2>\n\n\n\n
  • inhibit norepinephrine transporter\n(NET) and serotonin transporter (SERT) located at neuronal\/platelet membrane at\nlow and therapeutically attained concentrations.<\/li>
  • inhibit monoamine reuptake and\ninteract with a variety of receptors viz. muscarinic, \u03b1 adrenergic, histamine\nH1, 5-HT1, 5-HT2 and occasionally dopamine D2.<\/li><\/ul>\n\n\n\n

    Bupropion (atypical)\nalso inhibits dopamine reuptake<\/em>. NA and serotonin initially act on\npresynaptic <\/em>a2\nand 5HT1A receptors respectively and decrease the firing of locus ceruleus (NA)\nand nucleus raphe magnus (5HT). <\/p>\n\n\n\n

    • On long term administration,\ndesensitization of these receptors occurs and enhanced transmission is seen. <\/li>
    • This explains the long latency (2-3\nweeks) <\/em>for the anti-depressant action of TCA and SSRIs despite immediate inhibition\nof reuptake process.<\/li><\/ul>\n\n\n\n

      Adverse\nEffects<\/strong><\/p>\n\n\n\n

      \u2022 Sedative\n<\/strong>action of TCAs appears immediately and these drugs (particularly clomipramine,\nmaprotiline and bupropion) lower the seizure threshold.<\/strong><\/p>\n\n\n\n

      \u2022 Weight\ngain <\/strong>is another problem with the use of <\/strong>TCAs.<\/p>\n\n\n\n

      \u2022 Most TCAs possess powerful anticholinergic and weak <\/strong>\u03b1 blocking properties<\/strong>.<\/p>\n\n\n\n

      Overdose\nmanifestations are mainly anticholinergic (delirium, urinary retention, blurred\nvision and constipation) in nature. <\/p>\n\n\n\n

      These also\ncause postural hypotension (due to \u03b1 blockade) and cardiac arrythmias at toxic\nlevels.<\/p>\n\n\n\n

      \u2022 TCAs\nhave low safety margin<\/strong>.<\/p>\n\n\n\n

      \u2022 Amoxapine\n<\/strong>acts by blocking D2 receptors <\/strong>in addition to the inhibition of NA reuptake.\nIt possesses antipsychotic properties as well <\/strong>(It is a metabolite of antipsychotic\ndrug; loxapine). However, risk of extrapyramidal symptoms and convulsions is\nalso present.<\/p>\n\n\n\n

      \u2022 TCAs <\/em>(impiramine<\/em>) are also indicated for nocturnal enuresis in children <\/em>(However, DOC is desmopressin)<\/strong>.<\/em><\/p>\n\n\n\n

      \"\"<\/figure><\/div>\n\n\n\n

      Tolerance<\/strong> to the anticholinergic and hypotensive effects of imipramine-like drugs develops gradually, but antidepressant action is sustained.<\/p>\n\n\n\n

      2. Selective Serotonin Reuptake Inhibitors (SSRI)<\/h2>\n\n\n\n
      • These drugs inhibit the reuptake of 5-HT\nonly <\/strong>(not NA) and lack anticholinergic and \u03b1 blocking properties. <\/li>
      • SSRIs are now the first-choice\ndrugs <\/strong>for depression, phobias, OCD, PTSD, bulimia, premenstrual tension\nsyndrome and panic attacks <\/em>because they offer several advantages over TCAs:<\/li><\/ul>\n\n\n\n

        \u2022 No\nanticholinergic adverse effects<\/p>\n\n\n\n

        \u2022 No\nsedation or weight gain<\/p>\n\n\n\n

        \u2022 No\npropensity to cause seizures or arrhythmias<\/p>\n\n\n\n

        • They are devoid of \u03b1 adrenergic\nblocking action\u2014postural hypotension does not occur, making them<\/li><\/ul>\n\n\n\n

          suitable\nfor elderly patients.<\/p>\n\n\n\n

          SSRIs are\npreferred for prophylaxis of recurrent depression (should be combined with\nlithium\/valproate)<\/strong><\/p>\n\n\n\n

          Metaanalysis of comparative trials has shown no significant difference in\nefficacy among individual SSRI<\/p>\n\n\n\n

          Important\ncompounds<\/strong><\/p>\n\n\n\n

          \u2022 Fluoxetine<\/strong>:\nIt is a prototype SSRI and is longest acting <\/strong>drug in this group. It is metabolized\nto nor-fluoxetine that retains the anti-depressant activity.<\/p>\n\n\n\n

          • Because of slower onset of\nantidepressant effect, it is considered less suitable for patients needing\nrapid effect<\/li><\/ul>\n\n\n\n

            \u2022 Fluvoxamine\n<\/strong>is the shortest acting <\/strong>SSRI.<\/p>\n\n\n\n

            • specifically recommended for\ngeneralized anxiety disorder and OCD, rather than for depression<\/li><\/ul>\n\n\n\n

              \u2022 Paroxetine,\nsertraline <\/strong>and citalopram <\/strong>are other SSRIs.<\/p>\n\n\n\n

              \u2022 Escitalopram\n<\/strong>is most specific <\/em>SSRI.<\/p>\n\n\n\n

              \u2022 Paroxetine\nis most teratogenic among SSRIs.<\/strong><\/p>\n\n\n\n

              Dapoxetine\n<\/strong>A SSRI which has been developed and is\nbeing promoted for delaying premature ejaculation, a property<\/p>\n\n\n\n

              Dapoxetine acts rapidly and can be taken 1 hour before sexual\nintercourse.<\/p>\n\n\n\n

              Combined with behavioural therapies, it has been found to help many\nsufferers<\/p>\n\n\n\n

              Adverse\neffects<\/strong><\/p>\n\n\n\n

              • Prominent side effects are gastrointestinal; all SSRIs frequently produce nausea (due to 5-HT3 receptor stimulation), but tolerance develops over time.<\/li>
              • Loose motions are due to 5-HT uptake blockade in the gut and activation of 5-HT receptors on<\/li>
              • enteric plexus neurones. <\/li>
              • Weight gain is not a problem with SSRIs, but they more commonly interfere with ejaculation or orgasm.<\/strong><\/li>
              • Coadministration of SSRIs with MAO inhibitors can result in serotonin syndrome<\/em>. SSRIs can cause akathisia. <\/li>
              • Because SSRIs affect platelet serotonin levels, abnormal bleeding can occur.<\/li>
              • Sertraline and citalopram appear to be safest SSRIs to be used with warfarin<\/em>.<\/li><\/ul>\n\n\n\n

                Serotonin syndrome\u2019 manifesting as agitation, restlessness, rigidity, hyperthermia, delirium, sweating, twitchings followed by convulsions can be precipitated when any serotonergic drug (e.g. MAOIs, tramadol, pethidine) is taken by a patient receiving SSRIs.<\/p>\n\n\n\n

                3. MAO Inhibitors<\/h2>\n\n\n\n

                Two types\nof monoamine oxidase enzymes (MAO-A and MAO-B) are involved in the metabolism\nof monoamines.<\/p>\n\n\n\n

                \u2022 MAO-A\n<\/strong>predominantly metabolizes NA, 5-HT and DA <\/strong>and is present in the intestine,\nperipheral nerve endings and liver. \u00e0\nClorgyline, Moclobemide<\/strong> <\/p>\n\n\n\n

                \u2022 MAO-B\n<\/strong>preferentially metabolizes dopamine <\/strong>and is present in the brain,\nplatelets and liver.<\/p>\n\n\n\n

                Non\nselective MAO inhibitors<\/strong><\/p>\n\n\n\n

                Tranylcypromine,\nisocarboxazid and phenelzine <\/strong><\/p>\n\n\n\n

                inhibits\nboth isoforms of MAO irreversibly. \u00e0\nHIT and RUN drugs<\/p>\n\n\n\n

                Their\nanti-depressant effect takes 3-4 weeks to develop. <\/p>\n\n\n\n

                These\ndrugs exhibit a large number of drug and food interactions. The important ones\nare:<\/p>\n\n\n\n

                Selective\nMAO -B inhibitors<\/strong><\/p>\n\n\n\n

                Selegiline <\/strong>inhibits only MAO-B and is useful in Parkinsonism<\/strong>. It is available as a transdermal<\/em> patch <\/em>for treatment of depression.<\/p>\n\n\n\n

                \u2022 Cheese\nreaction<\/strong>: <\/p>\n\n\n\n

                Cheese,\nbeer and red wine, pickled meat and fish contain tyramine <\/em>(indirectly\nacting sympathomimetic). <\/p>\n\n\n\n

                Normally\nit is metabolized by MAO-A present in the intestine and is not absorbed. <\/p>\n\n\n\n

                In persons\ntaking non-selective MAO inhibitors, tyramine escapes degradation and can lead\nto hypertensive crisis<\/strong>. It is known as cheese reaction. <\/p>\n\n\n\n

                So, cheese\netc. should not be given to patients on long term non selective MAO inhibitor\ntherapy. <\/p>\n\n\n\n

                Phentolamine\n(alpha blocker) <\/strong>is the drug of choice for cheese reaction.<\/p>\n\n\n\n

                Prazosin\nor chlorpromazine are alternatives.<\/p>\n\n\n\n

                \u2022\nNon-selective MAO inhibitors increase the risk of seizures <\/strong>if given\nalong with pethidine due to enhanced generation of excitatory metabolite\nnor-meperidine.<\/p>\n\n\n\n

                \u2022 Serotonin\nsyndrome<\/strong>: <\/p>\n\n\n\n

                If given\nalong with or just after discontinuation of MAO inhibitors, SSRIs <\/strong>can\nresult in serotonin syndrome. <\/p>\n\n\n\n

                To avoid this fatal condition, SSRIs should be started at least 14\ndays after discontinuation of MAO inhibitors.<\/strong><\/p>\n\n\n\n

                It allows\nsufficient time for regeneration of MAO.<\/p>\n\n\n\n

                Reversible\ninhibitors of MAO -A (RIMA )<\/strong><\/p>\n\n\n\n

                • Moclebemide<\/strong>\ninhibits MAO-A selectively and reversibly. Because of its reversible and short action,\n<\/li>
                • it does not exhibit cheese reaction\n<\/strong>with foods. <\/li>
                • It lacks the anticholinergic,\nsedative, cognitive, psychomotor and cardiovascular adverse effects of typical\nTCAs and is safer in overdose.<\/li>
                • Particularly good option in elderly\npatients and in those with heart disease.<\/li><\/ul>\n\n\n\n

                  It can be\nused as an alternative to TCAs for the treatment of depression.<\/p>\n\n\n\n

                  B. Atypical Antidepressants<\/h1>\n\n\n\n

                  These\ndrugs may or may not increase monoaminergic levels and possess different\nantidepressant mechanisms.<\/p>\n\n\n\n

                  \u2022 Trazodone\n<\/strong><\/p>\n\n\n\n

                  prominent\n\u03b1 blocker and weak 5-HT2 antagonist. <\/p>\n\n\n\n

                  It\nproduces sedation, priapism <\/em>(prolonged\nand painful erection) and postural hypotension<\/em><\/strong>as adverse\neffects.<\/p>\n\n\n\n

                  \u2022 Mianserin\n<\/strong><\/p>\n\n\n\n

                  acts by blocking\npresynaptic <\/strong>a2\nreceptors <\/strong>but seizure <\/em>augmenting and bone\nmarrow depressant <\/em>actions restrict its use.<\/p>\n\n\n\n

                  \u2022 Tianeptin\nand amineptine <\/strong>acts by enhancing <\/strong>the serotonin reuptake (action opposite\nto SSRI<\/em>).<\/p>\n\n\n\n

                  \u2022 Venlafaxine,\nmilnacipran, levo-milnacipran and duloxetine <\/strong>inhibit reuptake of serotonin\nand NA but lack anticholinergic and <\/strong>a blocking properties<\/strong>.\n<\/p>\n\n\n\n

                  These are\nalso referred to as serotonin and nor-adrenaline reuptake inhibitors (SNRI<\/strong>).<\/p>\n\n\n\n

                  Venlafaxine\nhas faster onset <\/strong>of action. It has minimum drug-drug interactions.<\/em><\/p>\n\n\n\n

                  \u2022 Mirtazapine:\n<\/strong><\/p>\n\n\n\n

                  It\ninhibits presynaptic a2\nreceptors and thus increases NA and 5-HT release due to inhibition of auto- and\nhetero-receptors respectively. <\/p>\n\n\n\n

                  Although it\nincreases serotonin levels in synapse, there is selective activation of 5-HT1 receptors\ndue to antagonistic activity at 5-HT2 and 5-HT3 receptors. <\/p>\n\n\n\n

                  Therefore\nit is also known as nor-adrenergic and specific serotonergic anti-depressant\n<\/strong>(NSSA).<\/p>\n\n\n\n

                  It has minimal\nsexual side effects <\/strong>compared with SSRIs. It commonly causes sedation,\nweight gain, lipid abnormalities and dizziness.<\/p>\n\n\n\n

                  \u2022 Bupropion:\n<\/strong><\/p>\n\n\n\n

                  It\ninhibits the uptake of NA and DA. <\/p>\n\n\n\n

                  It is\nmetabolized to amphetamine like compound and possesses excitatory property. <\/p>\n\n\n\n

                  It is used\nfor smoking cessation <\/strong>as sustained release formulation. <\/p>\n\n\n\n

                  It can\nprecipitate seizures <\/strong>at high dose.<\/p>\n\n\n\n

                  \u2022 Nafazodone:\n<\/strong><\/p>\n\n\n\n

                  It blocks\nserotonin reuptake and antagonizes 5-HT2 receptors. <\/p>\n\n\n\n

                  It lacks\nanticholinergic effects (of TCAs) and agitation (seen with SSRI). <\/p>\n\n\n\n

                  It has\nvery short half life and is hepatotoxic.<\/p>\n\n\n\n

                  \u2022 Atomoxetine:\n<\/strong>It is a selective inhibitor of NA reuptake and is useful for Attention Deficit\nHyperkinetic Disorder <\/strong>(efficacy similar to methylphenidate).<\/p>\n\n\n\n

                  \u2022 Duloxetine <\/strong>(a mixed NA and 5HT reuptake inhibitor) is also useful in treating chronic neuropathic pain e.g. in diabetic neuropathy and fibromyalgia.<\/strong><\/p>\n\n\n\n

                  \"\"<\/figure><\/div>\n\n\n\n

                  USES<\/h1>\n\n\n\n
                  1. Endogenous (major) depression:<\/em><\/strong> <\/li><\/ol>\n\n\n\n
                    • The aim is to relieve symptoms of depression and restore normal social behaviour. <\/li>
                    • The tricyclic and related antidepressants are of proven value. <\/li>
                    • Response takes at least 2\u20133 weeks to appear, full benefits take still longer. <\/li>
                    • Choice of a particular drug for an individual patient depends on the secondary properties (sedative, anticholinergic, hypotensive, cardiotoxic, seizure precipitating, etc.)<\/li>
                    • The SSRIs are currently used as first choice for their better tolerability, safety and maybe higher efficacy as well. <\/li>
                    • The SNRIs and newer atypical agents also offer some advantages. <\/li>
                    • The only antidepressants clearly shown to be effective in juvenile depression are fluoxetine and sertraline. <\/li>
                    • The TCAs are mostly used as alternatives in non-responsive cases or in those not tolerating the second generation antidepressants.<\/li>
                    • Moclobemide is a well tolerated option for mild to moderate depression, especially suited for elderly and cardiac patients<\/li>
                    • Discontinuation of the antidepressant may be attempted after 6\u201312 months. <\/li>
                    • ECT may be given in the severely depressed, especially initially while the effect of antidepressants is developing, because no antidepressant has been clearly demonstrated to act fast enough to prevent suicide. <\/li>
                    • The TCAs or SSRIs must be combined with lithium\/valproate\/lamotrigine for bipolar depression, and not used alone due to risk of switching over to mania.<\/li><\/ul>\n\n\n\n

                      2. Obsessive-compulsive and phobic states:<\/em><\/strong><\/p>\n\n\n\n

                      • The SSRIs, particularly fluoxamine,\nare the drugs of choice due to better patient acceptability.<\/li>
                      • TCAs, especially clomipramine, are\nhighly effective in OCD and panic disorders: more than 25% improvement occurs\nin OCD rating scale and panic attacks are reduced in >75% patients.<\/li>
                      • SSRIs and TCAs also reduce compulsive\neating in bulimia<\/em>, and help patients with body dysmorphic disorder,\ncompulsive buying <\/em>and kleptomania, <\/em>though these habits may not completely\ndie.<\/li><\/ul>\n\n\n\n

                        3. Anxiety disorders:<\/em><\/strong> <\/em><\/p>\n\n\n\n

                        • Antidepressants, especially SSRIs,\nexert a delayed but sustained beneficial effect in many patients of generalized\nanxiety disorder; <\/em>may be used along with a short course of BZDs to cover\nexacerbations. <\/li>
                        • SSRIs\nhave also proven helpful in phobic disorders<\/em>, sustained treatment of panic\nattacks <\/em>and in posttraumatic stress disorder.<\/em><\/li><\/ul>\n\n\n\n

                          4. Neuropathic pain:<\/em><\/strong> <\/em><\/p>\n\n\n\n

                          • Amitriptyline and other TCAs afford\nconsiderable relief in diabetic and some other types of chronic pain. <\/li>
                          • Amitriptyline reduces intensity of\npost-herpetic neuralgia in ~50% patients. <\/li>
                          • The SSRIs are less effective in these conditions.\n<\/li>
                          • Duloxetine,\na SNRI, is now a first line drug for diabetic neuropathy, fibromyalgia, etc.\nOther drugs useful in neuropathic pain are pregabalin or gabapentin. <\/li><\/ul>\n\n\n\n

                            5. Attention deficit-hyperactivity disorder (ADHD) in children:<\/em><\/strong>\n<\/em><\/p>\n\n\n\n

                            • TCAs with less depressant properties\nlike imipramine, nortriptyline and amoxapine are now first line drugs in this\ndisorder, comparable in efficacy to amphetamine like drugs, with the advantage\nof less fluctuating action and fewer behavioural side effects.<\/li><\/ul>\n\n\n\n

                              6. Premature ejaculation:<\/em><\/strong> <\/em><\/p>\n\n\n\n

                              • Most SSRIs and some TCAs, especially clomipramine\nhave the common property of delaying and in some cases inhibiting ejaculation (this\nitself can cause sexual distress). <\/li>
                              • The primary treatment of premature\nejaculation is counselling and behavioural therapy, but this can be\nsupplemented by drugs. <\/li>
                              • Dapoxetine is a SSRI which has been\nspecifically introduced for this purpose. It acts rapidly; 60 mg taken 1 hour before\nintercourse has helped many subjects.<\/li><\/ul>\n\n\n\n

                                7. Enuresis:<\/em><\/strong> <\/em><\/p>\n\n\n\n

                                • In children above 5 years, imipramine 25 mg at bedtime is effective, but bed wetting may again start when the drug is stopped.<\/li>
                                • Elderly subjects with bed wetting have also benefited.<\/li><\/ul>\n\n\n\n

                                  8. Migraine:<\/em><\/strong> <\/em>Amitriptyline\nhas some prophylactic value, especially in patients with mixed headaches.<\/p>\n\n\n\n

                                  9. Pruritus<\/em>:<\/strong> Some tricyclics have antipruritic action.\nTopical doxepin has been used to relieve itching in atopic dermatitis, lichen\nsimplex, etc.<\/p>\n","protected":false},"excerpt":{"rendered":"

                                  Antidepressant Drugs Depression results due to decreased monoaminergic (5-HT and NA) activity in the brain, therefore drugs increasing their activity are called typical anti-depressants. Drugs acting by other mechanisms are called atypical anti-depressants. A. Typical Antidepressants Drugs may increase monoaminergic transmission by inhibiting the reuptake or metabolism of 5-HT or NA. 1. Tricyclic Antidepressants (TCA)[…]\n","protected":false},"author":3,"featured_media":150,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[13],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/148"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=148"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/148\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/150"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=148"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=148"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=148"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}