Zoloft®: composition and pharmaceutical form
Zoloft® comes as film-coated tablets containing 50 mg or 100 mg of sertraline as the hydrochloride.
The medicine is taken once a day, in the morning or the evening, with or without food. The two strengths make it possible both to raise the dose in 50 mg steps and to lower it just as smoothly when the course ends.
How Zoloft® works
Sertraline is a potent and specific inhibitor of serotonin uptake by nerve cells; at therapeutic doses it also blocks serotonin uptake by human platelets. On the reuptake of noradrenaline and dopamine it has only a very weak effect and it does not touch catecholaminergic transmission.
Its selectivity also explains the tolerance profile: sertraline has no affinity for muscarinic cholinergic, serotonin, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. In animal studies it showed no stimulant, sedative, anticholinergic or cardiotoxic action, and in healthy volunteers it caused no drowsiness and did not impair psychomotor function.
Indications
Zoloft® is used in episodes of major depression and to prevent their recurrence, in panic disorder with or without agoraphobia, in social anxiety disorder and in post-traumatic stress disorder.
Obsessive-compulsive disorder is singled out: here the medicine is prescribed not only to adults but also to children and adolescents aged 6 to 17. At the same time the efficacy of sertraline in major depression in children is not proven, and on use in children under 6 there are no data at all.
Method of use and dosage
The starting dose depends on the diagnosis: in anxiety disorders treatment begins with a lower dose to reduce the frequency of adverse reactions at the start of therapy. The dose is changed no more often than once a week — the half-life of sertraline is about 24 hours.
| Indication or situation | Dose |
|---|---|
| Depression and obsessive-compulsive disorder | start with 50 mg a day |
| Panic disorder, PTSD, social anxiety disorder | start with 25 mg a day and after a week raise to 50 mg |
| Increasing the dose | in 50 mg steps with an interval of at least a week, a maximum of 200 mg a day |
| Children aged 6–12 with OCD | start with 25 mg and after a week move to 50 mg; then as needed, a maximum of 200 mg |
| Adolescents aged 13–17 with OCD | start with 50 mg a day |
| Hepatic impairment | lower doses or less frequent dosing; in severe impairment the medicine is not used |
| Withdrawal of the medicine | gradual reduction, over at least 1–2 weeks |
The first signs of action are possible as early as 7 days, but the full effect usually takes longer, especially in obsessive-compulsive disorder. In depression treatment continues for at least 6 months after symptoms disappear; in panic disorder and OCD the need to continue is reviewed regularly, since the medicine's ability to prevent relapses in those diagnoses is not proven. In renal impairment the dose is unchanged, and in the elderly caution is needed because of the raised risk of hyponatraemia. When raising the dose above 50 mg in children their lower body weight is taken into account.
Contraindications
There are few contraindications and all of them relate to the risk of serotonin syndrome.
- hypersensitivity to sertraline or to any excipient;
- concomitant use of irreversible MAO inhibitors — the combination threatens serotonin syndrome with psychomotor agitation, muscle tremor and hyperthermia;
- sertraline may be started no earlier than 14 days after treatment with an irreversible MAO inhibitor ends;
- sertraline is withdrawn at least 7 days before treatment with an irreversible MAO inhibitor begins;
- concomitant use of pimozide: sertraline raised its concentration by about 35%, and the therapeutic index of pimozide is narrow.
Special warnings and precautions
Depression carries an increased risk of suicidal thoughts, self-harm and suicide, and the risk persists until full remission. Improvement may not come in the first weeks of treatment or later, so until it appears the patient is watched with particular care; clinical experience shows the risk can rise in the early phase of recovery. The same precautions apply in the other psychiatric disorders for which the medicine is prescribed — they are often combined with severe depression.
Serotonin syndrome and neuroleptic malignant syndrome
In patients taking medicines of this group the development of potentially life-threatening states has been described — serotonin syndrome and neuroleptic malignant syndrome. The risk rises with concomitant use of other serotonergic agents, including antidepressants and triptans, of medicines that disturb serotonin metabolism (among them MAO inhibitors and methylene blue), of antipsychotics and other dopamine antagonists, and of opioids. The patient is monitored for signs of these syndromes. Caution is also needed when switching to sertraline from other antidepressants, especially long-acting ones such as fluoxetine.
Other warnings
- combination with tryptophan, fenfluramine, 5-HT agonists and St John's wort is avoided where possible because of pharmacodynamic interactions;
- cases of QTc interval prolongation and torsade de pointes have been described, so with risk factors for QTc prolongation the medicine is used cautiously;
- in some patients mania or hypomania was observed: with such episodes in the history strict monitoring is needed, and if a manic phase develops the medicine is withdrawn;
- in patients with schizophrenia psychotic symptoms may intensify;
- in unstable epilepsy the medicine is not used, in controlled epilepsy the patient is watched closely, and if seizures occur it is withdrawn;
- the patient and those close to them are warned to contact a doctor immediately if symptoms worsen, suicidal thoughts appear or behaviour becomes unusual;
- in the elderly the risk of hyponatraemia is higher;
- alcohol should be avoided during treatment.
Drug interactions
Sertraline must not be combined with irreversible MAO inhibitors, for example selegiline, or with the reversible selective inhibitor moclobemide. Between withdrawal of an irreversible MAO inhibitor and the start of sertraline at least 14 days are left, and before starting treatment with an MAO inhibitor sertraline is withdrawn at least 7 days beforehand. Linezolid — a weak reversible non-selective MAO inhibitor — is not prescribed to patients on sertraline. When these intervals are not observed, severe reactions have been described: muscle tremor, myoclonus, profuse sweating, nausea and vomiting, reddening of the skin, dizziness, hyperthermia with features of neuroleptic malignant syndrome, seizures and death.
Caution is required with fentanyl, used in anaesthesia and in chronic pain, with other serotonergic agents and with opioids. The risk of QTc prolongation and ventricular arrhythmias grows in combination with other QTc-prolonging medicines — certain antipsychotics and antibiotics. With lithium no pharmacokinetic interaction has been found, but tremor intensified, so that combination calls for monitoring. As for phenytoin, its concentration is monitored at the start of treatment. Alcohol is not recommended during treatment.
Pregnancy and breastfeeding
There are no sufficient controlled studies in pregnant women. No congenital malformations caused by sertraline were seen in experiments, but animal studies showed an effect on reproduction — probably through pharmacodynamic action on the mother and direct action on the foetus. Use during pregnancy caused in some newborns symptoms consistent with a withdrawal syndrome; the same has been described for other medicines of this group. The medicine is not recommended in pregnancy unless the woman's condition justifies such a need and the benefit outweighs the risks.
If the mother continues taking the medicine late in pregnancy, especially in the third trimester, the newborn is monitored: acute respiratory failure, cyanosis, apnoea, convulsions, temperature swings, feeding difficulties, vomiting, hypoglycaemia, changes in muscle tone, brisk reflexes, tremor, irritability, continuous crying and sleep disturbances are possible. This usually occurs in the first day after delivery. The risk of persistent pulmonary hypertension of the newborn is estimated at about 5 cases per 1000 pregnancies against 1–2 in the general population. Sertraline and its metabolite pass into breast milk in small amounts, and in children their serum concentrations are usually very low or undetectable; no adverse events have been described in such children, but they cannot be ruled out, so the medicine is prescribed to breastfeeding women only if the benefit outweighs the risk.
Adverse effects
The most frequent adverse reaction is nausea. In the treatment of social anxiety disorder, sexual dysfunction, in particular the inability to ejaculate, was recorded in 14% of men against 0% on placebo; such reactions are dose-dependent and often pass if treatment continues.
- common: insomnia, dizziness, drowsiness, headache, nausea, decreased or increased appetite, visual disturbances, tinnitus, pharyngitis;
- common in the psychic sphere: depression, depersonalisation, nightmares, anxiety, agitation, nervousness, reduced libido, bruxism;
- uncommon: sensory disturbances, tremor, increased tone, disturbances of taste and concentration, seizures, involuntary muscle movements, disturbances of coordination and memory, speech disorders, fainting, migraine, pupil dilation, hypothyroidism, upper respiratory tract infections;
- uncommon in the psychic sphere: hallucinations, aggression, euphoria, apathy, thought disorders;
- rare: coma, choreoathetosis, dyskinesia, glaucoma, double vision, anaphylactic reactions, hypoglycaemia, suicidal thoughts and behaviour, paranoia, drug dependence;
- frequency not known: hyponatraemia, hyperglycaemia, hyperprolactinaemia, impaired secretion of antidiuretic hormone, leucopenia, thrombocytopenia;
- frequency not known: movement disorders, including extrapyramidal ones — hyperkinesia, hypertonia, dystonia, gait disturbances — as well as akathisia and spasm of the cerebral vessels.
Signs of serotonin or neuroleptic malignant syndrome — agitation, confusion, profuse sweating, diarrhoea, fever, raised blood pressure, rigidity, tachycardia — were in a number of cases linked to the concomitant use of other serotonergic agents. Abrupt withdrawal of the medicine risks withdrawal symptoms, so the dose is lowered gradually.
Overdose
The safety margin depends on the patient's condition and on what other medicines they had taken. Fatal outcomes from sertraline overdose have been described — both alone and in combination with other medicines or with alcohol — so any case requires intensive medical intervention.
The symptoms repeat the adverse effects: drowsiness, nausea and vomiting, tachycardia, tremor, agitation and dizziness; coma was described less often. QTc interval prolongation and torsade de pointes have also been reported, so ECG monitoring is necessary. There is no specific antidote. A patent airway and sufficient oxygenation and ventilation are ensured; activated charcoal, including with a laxative, is no less effective than gastric lavage and should be considered first, while inducing vomiting is not recommended. Cardiac function and the main vital signs are monitored and symptomatic and supportive treatment is given. Because of sertraline's large volume of distribution, forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be effective.
How to get a prescription for Zoloft® online
Zoloft® is a prescription-only medicine: the doctor chooses the starting dose by diagnosis, sets the pace of increase and the length of the course, and checks compatibility with other medicines — from MAO inhibitors to agents affecting the QT interval.
During the online consultation the doctor will clarify the symptoms, go through the medicines you take and assess contraindications. If the medicine is suitable, they will issue an electronic prescription and explain what to expect in the first weeks and how to finish treatment properly so as to avoid withdrawal symptoms.
