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.Theyalso seem to interfere with the process of extinction, biologically byreducing long-term potentiation necessary for unlearning the fear [2], aswell as psychologically, by lowering one s willingness to endure anxietywhen exposed unmedicated to the feared situation [7].Antidepressantsreduce phobic anxiety and improve patient s functions through severalmechanisms.Antidepressants with norepinephrine or serotonin reuptakeinhibitory properties block panic attack and, therefore, eliminate the initialcause of agoraphobia.They probably also reduce to some degree the panic-like surge of anxiety in other phobias when a person is exposed to thephobic situation.However, when studying agoraphobic patients with panicattacks, Mavissakalian et al.found imipramine but not norepinephrineplasma levels related to improvement of agoraphobia [8].Imipramine hasnorepinephrine and serotonin reuptake inhibitory properties, whiledesipramine predominantly inhibits norepinephrine reuptake.We alsofound imipramine but not desipramine blood levels associated with anxietyreduction in patients with generalized anxiety disorder [9].In a recentimaging study, we observed in patients with generalized anxiety disorderthat anxiety reduction with the SRI citalopram reduced excessive brainactivation to specific symptom provocation as well as to non-specific stimuli[10].It appears that SRIs reduce the general level of anxiety by lowering apatient s disproportionate sensitivity to external and internal stimuli.Inaddition, SRIs may induce an emotional indifference toward the stimuli,possibly by attenuating frontal lobe activity [11].For these reasons, SRIsappear to be more effective than other antidepressants in reducing psychic,including phobic, anxiety.With less anxiety, patients can confront fearedsituations, which leads to a gradual desensitization.The observation thatphobic patients continue to improve over 12 weeks and longer suggests agradual unlearning process.The long-term effectiveness of therapy depends on biological andpsychological factors.We need to explore the effects of new drugs but inaddition address, in smaller hypothesis-driven studies, questions that arefrequently ignored in larger studies.For instance, why do some but notother patients respond to certain medications or treatments? Pharmacoge-netic studies may provide some answers.Can we develop drugs thatenhance learning, leading to faster desensitization? What are the effects ofdrugs on patients who improve only partially? Why do some but not otherpatients relapse after discontinuation of medications? In these patients,does generalized anxiety re-emerge after discontinuation of medications,which reactivates phobic fears? To what degree does the desensitization ofphobias, including residual phobias in drug-treated patients, depend onpatients motivation to overcome fears and on their personality traits? Theseare some questions than need to be explored.148 __________________________________________________________________________________________ PHOBIASREFERENCES1.Kendler K.S., Neale M.C., Kessler R.C., Heath A.C., Eaves L.J.(1992) Thegenetic epidemiology of phobias in women: the interrelationship of agora-phobia, social phobia, situational phobia, and simple phobia.Arch.Gen.Psychiatry, 49: 273 281.2.Davis M.(1992) The role of the amygdala in conditioned fear.In The Amygdala(Ed.J.P.Aggleton), pp.255 305.Wiley-Liss, New York.3.Kraepelin E.(1914) Psychiatrie, 8th edn.Barth, Leipzig.4.Freud S.(1919) Turnings in the world of psychoanalytic therapy.In CollectedPapers, vol.2, pp.399 400.Hogarth Press, London.5.Marks I.(1987) Fears, Phobias and Rituals.Oxford University Press, New York.6.Lader M.H., Gelder M.G., Marks I.M.(1967) Palmar skin conductancemeasures as predictors of response to desensitization.J.Psychosom.Res., 11:283 290.7.Laughren T.P., Dias A.M., Keene C., Greenblatt D.J.(1986) Can chronicallyanxious patients learn to cope without medications? McLean Hosp.J., 11: 72 78.8.Mavissakalian M., Perel J.M., Michelson L.(1984) The relationship of plasmaimipramine and N-desmethylimipramine to improvement in agoraphobia.J.Clin.Psychopharmacol., 4: 36 39.9.McLeod D.R., Hoehn-Saric R., Porges S.W., Kowalski P.A., Clark C.M.(2000)Therapeutic effects of imipramine are counteracted by its metabolite,desipramine, in patients with generalized anxiety disorder.J.Clin.Psycho-pharmacol., 20: 615 621.10.Hoehn-Saric R., Schlund M.W., Wong S.H.Y.(submitted) Effect of citalopramon patients with generalized anxiety disorder: an imaging study.11.Hoehn-Saric R., Lipsey J.R., McLeod D.R.(1990) Apathy and indifference inpatients on fluvoxamine and fluoxetine.J.Clin.Psychopharmacol., 10: 343 345.3.3The Neuropsychology of Defence:Implications for Syndromes and PharmacotherapyNeil McNaughton1Social phobia, agoraphobia and simple phobia are all normally termed  phobia  , i.e.fear.Yet all are DSM   anxiety disorders .This confound isclear in the   pharmacotherapy of phobias  when Stein et al.refer to   socialphobia (or social anxiety disorder) .I argue that the   pharmacotherapy ofphobias  will be clearer if we apply neuroscientific theory [1].From a basicscience perspective, fear and anxiety are functionally, neurally andpharmacologically distinct.On this view, simple phobia is correctlynamed.However, much of the phenomenology of social phobia is best1Department of Psychology, University of Otago, P.O.Box 56, Dunedin, New ZealandPHARMACOTHERAPY OF PHOBIAS: COMMENTARIES _____________________________ 149thought of as social anxiety.Agoraphobia itself should strictly be renamed  agoranxiety .But, to confuse the issue, its treatment normally targetspanic, a primarily phobic entity, rather than agoraphobia itself.Entities that are functionally, neurologically and pharmacologicallydistinct in the laboratory are, nonetheless, frequently comorbid in theclinic.This occurs for two reasons.First, one clinical entity can, over time,result in another.Recurring panic can give rise to agoraphobia; chronicanxiety can give rise to depression.Second, genetics, personality and stress,as predisposing factors to morbidity, operate on pituitary adrenal andmonoamine systems that modulate the entire defence system.Theoccurrence of a specific disorder (or chronic stress) can   kindle  sensitivityto neurotic disorders in general [2 4].Despite comorbidity, the neurotic syndromes can be located [1] in a two-dimensional view of defensive systems (Table 3.3.1).The first dimension isthat of defensive direction.Anxiety (and anxiolytic drug action) involvesystems controlling approach into threatening situations (i.e.approachavoidance conflict) and assessment of risk [ Pobierz całość w formacie PDF ]