Get­ting anx­i­ety right

Financial Mirror (Cyprus) - - FRONT PAGE -

When re­searchers want to eval­u­ate the ef­fi­cacy of new anx­i­ety treat­ments, the tra­di­tional ap­proach is to study how rats or mice be­have in un­com­fort­able or stress­ful sit­u­a­tions. Ro­dents shun brightly lit, open spa­ces, where, in the wild, they would be­come easy prey. So their nat­u­ral ten­dency in a test ap­pa­ra­tus is to find ar­eas that are poorly il­lu­mi­nated or close to walls. The longer a med­i­cated an­i­mal spends in ar­eas in which it is un­pro­tected, the more ef­fec­tive the drug is judged to be in treat­ing anx­i­ety.

But the drugs that have re­sulted from this ap­proach are not ac­tu­ally very good at mak­ing peo­ple feel less anx­ious. Nei­ther pa­tients nor their ther­a­pists con­sider the avail­able op­tions – in­clud­ing ben­zo­di­azepines like Val­ium and selec­tive sero­tonin re­up­take in­hibitors like Prozac or Zoloft – as ad­e­quate treat­ments for anx­i­ety. Af­ter decades of re­search, some of the big phar­ma­ceu­ti­cal com­pa­nies are rais­ing the white flag and cut­ting back on ef­forts to de­velop new an­tianx­i­ety drugs.

But we can­not af­ford to give up on treat­ment for the so­called anx­i­ety dis­or­ders, which en­com­pass prob­lems re­lated to both fear and anx­i­ety. Feel­ings of fear oc­cur when a pos­si­ble source of harm is nearby or likely to present it­self, while feel­ings of anx­i­ety usu­ally in­volve the pos­si­bil­ity of harm in the fu­ture. World­wide, the life­time preva­lence of anx­i­ety dis­or­ders is about 15%, and the cost to so­ci­ety is enor­mous. In the late 1990s, it was es­ti­mated that the eco­nomic bur­den of anx­i­ety to­taled more than $40 bln. The to­tal cost is most likely sig­nif­i­cantly higher, be­cause many anx­i­ety dis­or­ders are never di­ag­nosed.

Counter-in­tu­itively, the rea­son that the most fre­quently pre­scribed anx­i­ety med­i­ca­tions don’t ad­dress the un­der­ly­ing prob­lem is that they are work­ing ex­actly as they should – ac­cord­ing to the cri­te­ria used to de­sign them. Most treat­ments based on stud­ies us­ing mice or rats do make anx­i­ety dis­or­ders eas­ier to live with. What they fail to do is ac­tu­ally make peo­ple less fear­ful or anx­ious.

The rea­son for this is sim­ple. The brain sys­tems that con­trol be­hav­ioral re­sponses in threat­en­ing sit­u­a­tions are sim­i­lar in ro­dents and hu­mans, and in­volve older ar­eas deep in the brain that work non­con­sciously (for ex­am­ple, the amyg­dala). On the other hand, the sys­tems that pro­duce con­scious ex­pe­ri­ences, in­clud­ing feel­ings of fear and anx­i­ety, in­volve evo­lu­tion­ar­ily new re­gions of the neo­cor­tex that are es­pe­cially well de­vel­oped in the hu­man brain and poorly de­vel­oped in ro­dents. Con­scious feel­ings are also de­pen­dent on our unique lin­guis­tic ca­pac­i­ties – our abil­ity to con­cep­tu­al­ize and name our in­ner ex­pe­ri­ences. It is telling that the English lan­guage has more than three dozen words for gra­da­tions of fear and anx­i­ety: worry, con­cern, ap­pre­hen­sion, un­ease, dis­qui­etude, in­qui­etude, angst, mis­giv­ing, ner­vous­ness, ten­sion, and so forth.

Con­se­quently, though an­i­mal stud­ies are use­ful in pre­dict­ing how a drug will af­fect non­con­sciously con­trolled symp­toms trig­gered by threat­en­ing stim­uli, they are less ef­fec­tive when it comes to con­scious feel­ings of fear or anx­i­ety. The drugs we have can help pa­tients who, in or­der to avoid sit­u­a­tions that in­spire fear or anx­i­ety, such as crowded sub­ways or be­ing judged by their peers or su­pe­ri­ors, have stopped go­ing to work. Just as med­i­cated rats are less be­hav­iorally in­hib­ited (more able to tol­er­ate bright, open spa­ces), med­i­cated anx­i­ety suf­fer­ers are more likely to be able to re­turn to their jobs. But, be­cause the treat­ments do not di­rectly ad­dress con­scious brain pro­cesses, the anx­i­ety it­self does not al­ways go away.

If treat­ments are to be­come more ef­fec­tive, our ap­proaches will need to be­come more nu­anced. We will need to treat the sys­tems that op­er­ate non­con­sciously dif­fer­ently from those that re­sult in con­scious ex­pe­ri­ences. This doesn’t nec­es­sar­ily mean bet­ter drugs. Non­con­scious re­sponses can also be treated with ex­po­sure ther­apy, in which re­peated in­ter­ac­tion with a threat­en­ing stim­u­lus is or­ches­trated in or­der to dampen its psy­cho­log­i­cal ef­fects.

Find­ings about how con­scious and non­con­scious brain sys­tems work may en­able us to make ex­po­sure ther­apy more ef­fec­tive. The ba­sic idea is that the symp­toms in­volv­ing non­con­scious pro­cesses should be tar­geted sep­a­rately from those in­volv­ing con­scious pro­cesses.

I sug­gest the fol­low­ing se­quence. Start with non­con­scious ex­po­sures (us­ing sub­lim­i­nal stim­u­la­tion to by­pass con­scious thoughts and feel­ings that can be aroused and in­ter­fere with the ex­po­sure process) to dampen the re­sponse of ar­eas like the amyg­dala. Once the non­con­scious sys­tems are un­der con­trol, use con­scious ex­po­sures to treat con­scious symp­toms. Fi­nally, em­ploy more tra­di­tional psy­chother­a­pies: Ver­bal in­ter­ac­tions with the ther­a­pist aimed at help­ing pa­tients work on chang­ing be­liefs, reeval­u­ate mem­o­ries, en­cour­age ac­cep­tance of one’s cir­cum­stances, ac­quire cop­ing strate­gies, and so on.

There is also a place for drugs in this ap­proach, but not as a long-term so­lu­tion. Rather, drugs can be used to make the ex­po­sure treat­ment more ef­fec­tive (the phar­ma­ceu­ti­cal d- cy­closer­ine has shown some prom­ise in this re­gard).

The ef­fec­tive­ness of an ap­proach that recog­nises that dif­fer­ent brain sys­tems con­trol dif­fer­ent symp­toms has yet to be prop­erly eval­u­ated, but re­search sug­gests that it should work. It would also be non­in­va­sive and would re­quire only a re­pur­pos­ing of fre­quently used pro­ce­dures. Given the mag­ni­tude of the prob­lem, a stone so eas­ily reached should not be left un­turned.

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