Curtailing clinicians’ prescribing choices

Among the antidepressants, list A includes only escitalopram and fluoxetine; the others are on list B. However, the evidence says that, among 21 antidepressants for the acute treatment of adults with major depressive disorder, escitalopram, paroxetine, amitriptyline, mirtazapine, venlafaxine, vortioxetine and agomelatine are more effective than other antidepressants, whereas fluvoxamine, trazodone, fluoxetine and reboxetine are the least efficacious. Tolerability and acceptability are higher for escitalopram, sertraline, citalopram, fluoxetine, agomelatine and vortioxetine than for the other antidepressants. Drop-out rates are higher for fluvoxamine, amitriptyline, clomipramine, venlafaxine, duloxetine, trazodone and reboxetine than for other antidepressants.^{Reference Cipriani, Furukawa, Salanti, Chaimani, Atkinson and Ogawa2}

The parallel is the case with antipsychotics. List A antipsychotics are risperidone, olanzapine and haloperidol only, while rest are under list B.^{Reference Math, Manjunatha, Kumar, Basavarajappa and Gangadhar1} Although in a given patient there may be some clinically meaningful differences in response due to individual differences in biological constitution and behaviour, to date there are no conclusive data that one second-generation antipsychotic will have superior efficacy over another (with clozapine in treatment-resistant schizophrenia as an exception).^{Reference Lehman, Lieberman, Dixon, McGlashan, Miller and Perkins3} A recent network meta-analysis of head-to-head randomised placebo-controlled trials comparing 32 antipsychotics found only minor efficacy differences between antipsychotics. There are marked differences among antipsychotics in terms of side-effects.^{Reference Huhn, Nikolakopoulou, Schneider-Thoma, Krause, Samara and Peter4} The right choice of an antipsychotic medication and the route of administration should be based on weighing the patient's previous experience with antipsychotics, the side-effect profile, response to symptoms and the patient's preference for a particular medication.^{Reference Lehman, Lieberman, Dixon, McGlashan, Miller and Perkins3,Reference Huhn, Nikolakopoulou, Schneider-Thoma, Krause, Samara and Peter4}

Let us ponder a possible clinical scenario where the patient has a history (more than 6 months) of good response to antidepressants other than escitalopram or fluoxetine or to antipsychotics other than risperidone, olanzapine and haloperidol; or a history of failed trials of escitalopram and fluoxetine for depressive disorders or list A antipsychotics for psychotic disorders/schizophrenia. The guidelines’ categorisation of psychotropics curtails the clinicians’ freedom to select the best medication for that patient.

Among anti-epileptic drugs, list A contains only phenobarbitone, diphenylhydantoin and sodium valproate, and there is only divalproex sodium on list B. A point to be noted here is that the list A medications are readily available, and hence keeping them on list A makes sense. On the other hand, data reflect that for treating generalised tonic–clonic, tonic and clonic seizures, levetiracetam, lamotrigine and topiramate are as effective as valproate. For absence seizures, valproate and ethosuximide are the best available treatment options.^{Reference Sadock and Sadock5} So, allowing only four anti-epileptics restricts the clinical choice of clinicians. Sodium valproate is on list A, whereas divalproex sodium is on list B. Each formulation of valproate is therapeutically equivalent because, at physiological pH, valproic acid dissociates into valproate ions.^{Reference de Almeida Campos, Ayres, Morelo, Carizio and Pereira6} Placement of the two preparations on different lists may not be warranted.

Is ‘add-on’ a misnomer?

As mentioned above, the medications on list B are described as ‘add-on’ medications, prescribed to optimise a particular psychiatric illness. List B antipsychotics such as aripiprazole, quetiapine, amisulpride and trifluoperazine have similar efficacy to olanzapine, risperidone and haloperidol, which are on list A. List B antidepressants and antipsychotics are similar to those on list A in terms of efficacy but differ in their tolerability.^{Reference Cipriani, Furukawa, Salanti, Chaimani, Atkinson and Ogawa2,Reference Huhn, Nikolakopoulou, Schneider-Thoma, Krause, Samara and Peter4} Thus, calling list B ‘add-on’ medications appears a misonmer.

If a psychiatrist is generating a prescription for injectable haloperidol, fluphenazine or promethazine in an online consultation with a registered medical practitioner, then these injectables are considered to be under list A, whereas in the same situation zuclopenthixol, flupentixol, paliperidone and aripiprazole are under list B. First-generation depot antipsychotics are cost-effective but second-generation depots are better tolerated,Reference Whyte and Parker⁷ but this is not reflected in their listing under this system. Moreover, depot olanzapine, considering its cost–benefit analysis, could be a list A medication.

Other drugs

It is not clear whether methylphenidate, a first-line agent in the management of attention-deficit hyperactivity disorder (ADHD), can be teleprescribed. It might be assumed that it is falls under ‘other drugs’ in list B (under anti-ADHD drugs). However, methylphenidate is listed in the Narcotic Drugs and Psychotropic Substances Act 1985 (NDPS). If we consider that it is approved under list B, an argument may arise that one drug under the NDPS has been approved whereas others (list C) are not. List C (teleprescription prohibited) contains drugs under schedule X of the Drugs and Cosmetics Act 1940 and Drugs and Cosmetics Rules 1945 and substances listed in the NDPS – morphine, buprenorphine, methadone, benzodiazepines (except clobazam and clonazepam!), Z-drugs such as zolpidem, and so on. Many high-income countries, the USA for example, have relaxed the rules to allow psychiatrists to evaluate patients via telephone or video calls before prescribing these medications.^{Reference Conolly8} India has twice the global average prevalence of illicit opioid consumption, with 23 million users.^{Reference Ambekar, Agrawal, Rao, Mishra, Khandelwal and Chadda9} A handful of them seek medical help. With such an inclusion, the barrier to help-seeking by people with substance use disorder may be magnified.

Psychotherapy

For psychotherapy, the ethics, legal provisions, accountability and responsibility requirements for teletherapy are similar to those for face-to-face therapy. Since the arrival of the pandemic on the Indian subcontinent, medical professionals have presented numerous virtual sessions for promotion of positive mental health, stress management, coping with the pandemic and similar issues. Nonetheless, as teletherapy carries certain limitations and therefore the guidelines advise a detailed initial face-to-face assessment. Even in detailed face-to-face assessment, a mask on the face of both the patient and the doctor impedes rapport, the transmission of empathy, the therapeutic alliance and outcome.^{Reference Wong, Yip, Mercer, Griffiths, Kung and Wong10} Such circumstances may be a barrier for some people who would like to choose psychotherapy as a modality of treatment. Of course, there are exceptions – behavioural therapies, for example, might be less affected by mask-wearing and tele-delivery.

Suicide and self-harm

Recent literature suggests that the number of people contemplating suicide and self-harm in India is rising.^{Reference Joseph11} Of course, modified electroconvulsive therapy (ECT) is the treatment of choice where suicidal intent is high.^{Reference Fink, Kellner and McCall12} But the silence of these guidelines on telepsychiatry for people who present with suicide and self-harm should not create uncertainty among clinicians if the clinical situation calls for its use.