ANXIETY AND DEPRESSION:PHARMACOTHERAPY

Dr Sanjay Sen MBBS(Cal) DPM(Dublin)

MRCPsych(London) CCST(UK) Consultant Psychiatrist,AMRI Hospitals

OUTLINE
In clinical terms,treatment of depression and anxiety are very alike These two overlap each other so much,its tough to demarcate at times which is the hen and which is the egg Indeed,they frequently give rise to the other and commonly coexist However,there are strict international protocols nowadays for their treatmentand believe me, I follow them

ANTIDEPRESSANTS
THE OBJECTIVE IS TO ENHANCE SEROTONERGIC TRANSMISSION NORADRENERGIC AND DOPAMINERGIC PATHWAYS PLAY IMPORTANT ROLE TOO THIS CAN BE ACHIEVED EITHER BY INCREASING SECRETION OR REDUCING REUPTAKE OF THESE IN THE SYNAPTIC CLEFT TILL DATE THERE ARE 4 CLASSES OF ANTIDEPRESSANTS AVAILABLE ,BASED ON THEIR MECHANISM OF ACTION(HOPE YOU WONT HARRASS ME ASKING STRUCTURAL DIFFERENCES!!)

CLASS-TRICYCLICS AND RELATED COMPOUNDS

INVENTED IN 50S(IMIPRAMINE) AND STILL REMAIN THE GOLD STANDARD IMIPRAMINE/AMITRYPTILINE/DOSULEPIN/LOFEPRA MINE/NORTRYPTILINE/CLOMIPRAMINE/TRIMIPRAMI NE/AMOXAPINE/MAPROTILINE/TRAZADONE/MIANSE RIN ETC ACT BY INHIBITING REUPTAKE OF BOTH SEROTONIN AND NORADRENALINE CLOMIPRAMINE IS MORE SEROTONIN SPECIFIC THAN THE REST EXTREMELY POTENT BUT RANGE OF INTOLERABLE SIDE EFFECTS,ALSO DANGEROUS IN OVERDOSES

TRICYCLICS-CONTD.
Some are more sedative than othersimipramine,nortryptiline and lofepramine are less sedative Serious side effects include arrhythmias,heart block and rarely sudden death in patients with pre-existing cardiac diseases.Convulsions can also occur in known epileptics Other side effects include anticholinergic effects which may become less troublesome with time.Hyponatraemia can rarely occur and neuroleptic malignant syndrome has been very rarely reported

Tricyclics-contd.
Tricyclics are most effective for treating moderate to severe endogenous depression associated with psychomotor and biological symptoms Other indications are panic disorder,OCD,neuralgic pains and nocturnal enuresis There is endless good quality evidence in their favour but since the advent of newer classes in 1990s,they have fallen out of favour as the preferred firstline drugs(some valid and some rubbish reasons)

Class-SSRIS
SSRI=Selective Serotonin Reuptake Inhibitor Fluoxetine,fluvoxamine,paroxetine,sertraline,cita lopram and escitalopram(isomer of citalopram) 1990s generation,box-office hit,very efficient marketing although SSRIs appear to be better tolerated than older drugs,the difference is too small to justify always choosing an SSRI as firstline treatment(British National Formulary Sept05) Safer in known patients with cardiac disease and in actively suicidal patients

SSRIS-CONTD.
They also have fewer anticholinergic side effects However,extensive research funded by drug companies worldwide has failed to show any advantage over tricyclics in terms of efficacy Indeed,in Britain they are licensed for mild and moderate depression Their main side effects appear to be upper GI and bowel upsets(caution in known peptic ulcer disease-may bleed).Others include,tremor,dry mouth,hyponatraemia,EPS,agitaion,galactorrhoe a,sexual dysfunction.They inhibit hepatic microsomal P450 system.

CLASS-MAOIS
Invented in 60s. Phenelzine,tranylcypromine,isocarboxazid No longer prescribed routinely because of dangerous interactions with several common drugs and dietary substances causing serotonin syndrome Only role in atypical depression and if depression is refractory to all other available measure

MAOIS-CONTD.
Any food containing tyramine will interact eg,mature cheese,pickled herring,broad bean pod,meat and yeast extracts,fermented soya,any old/processed meat fish poultry product,liver/offal,red wine,beer, Drugs like other antidepressants,many decongestants,cough mixtures,opioids,sympathomimetic amines and dopa,alcohol,even insulin!

MAOIS-CONTD.
Serotonin syndrome-dangerous rise in BP,neurotoxicity,high temp.,arrhythmias,death Other side effects include dry mouth,myoclonus,postural hypotension,headache,tremor,oedema weight gain and sexual dysfunction,hepatocellular jaundice Selective MAOI inhibitors(inhibiting only MAO A) are available eg. Moclobemide,reducing risks of serotonin syndrome

CLASS-MISCELLANEOUS
SNRIS-venlafaxin and duloxetine.Novel agents.At lower doses inhibit serotonin reuptake and at higher both serotonin and noradrenalin.Efficacy proven beyond doubt(equivalent to tricyclics) and better tolerated than tricyclics.Venlafaxin can raise BP and cause cardiac arrhythmias in patients with cardiac diseases.Other worrying side effect is weight gain Selective noradrenalin reuptake inhibitorreboxetine

MISC.-CONTD.
MIRTAZAPINE-a presynaptic alpha2 antagonist.Increases both serotonergic and noradrenergic neurotransmission.Potent compound.Fewer anticholinergic sideeffects.Initial sedation. The thioxanthine flupenthixol has antidepressaint properties and lower doses.Tryptophan is used in resistant depression but is associated with eosiniphillic myalgic syndrome

Treatment protocol for depression

Confirm diagnosis and start antidepressant from one class.Titrate up dose and review at 4-6 weeks.If effective,continue for 6 months. If first drug is not tolerated or ineffective,choose a second drug from another class.Titrate dose and review at 4-6 weeks.If effective continue treatment for 6 months.If not effective or tolerated,review diagnosis,confirm compliance and asses for comorbidity and drug interaction.If alls ok.consider your case to be refractory depression and treat likewise

Treatment protocol for refractory depression

Step 1- add lithium(pro-excellent evidence in favourcon-lots of hassles) Step 2- consider ECT(pro-excellent efficacy,good evidence..con-public stigma,general anaesthesia needed,not widely available here) Step 3- add T3/T4(pro-well tolerated,some evidence.con-blood tests) Step 4-add tryptophan(pro-well tolerated,some evidence.con-eosinophilic myalgic syndrome) Step 5- combination of two antidepressants

Refractory depression depressioncontd.

Step 6- add lamotrigine Step 7- add pindolol Step 8- combine olnazapine and fluoxetine

Special cases
Recurrent(i.e. more than 2 episodes) needs treatment for indefinite period,at least 5 years,preferably with an augmentation Psychotic depression needs an antipsychotic with antidepressant.ECT is very effective Depression has a 30% placebo effect CBT combined with antidepressant has better result than either alone.only for mild or moderate depression Despite all.10% patients will never respond No drug is safe in pregnancy and lactaing mothers

Treatment of anxiety disorders

OCD-SSRIs and clomipramine.Some evidence for antipsychotics/venlafaxin/buspirone/clonazepam GAD-SSRIS,venlafaxine and short term BDZ.Some evidence for buspirone/beta blockers/tiagabine Panic disorder-SSRIS and tricyclics like imipramine/clomipramine.Some evidence for MAOIS,mirtazapine,valproate,inositol PTSD-SSRI and clomipramine.Some evidence for MAOIS,valproate,CBZ,clonidine,tiagabine

Thank you.honestly!!